95715-87-0

Basic information

• Product Name: TERT-BUTYL (R)-(+)-4-FORMYL-2,2-DIMETHYL-3-OXAZOLIDINECARBOXYLATE
• Synonyms: TERT-BUTYL (R)-(+)-4-FORMYL-2,2-DIMETHYL-3-OXAZOLIDINECARBOXYLATE;TERT-BUTYL-(R)-4-FORMYL-2,2-DIMETHYL-3-OXAZOLIDINECARBOXYLATE;(R)-4-FORMYL-2,2-DIMETHYL-OXAZOLIDINE-3-CARBOXYLIC ACID TERT-BUTYL ESTER;(R)-(+)-3-BOC-2,2-DIMETHYL-OXAZOLIDIN-4-CARBALDEHYDE;(R)-3-BOC-4-FORMYL-2,2-DIMETHYL-1,3-OXAZOLIDINE;1,1-DIMETHYLETHYL-(R)-4-FORMYL-2,2-DIMETHYL-3-OXAZOLIDINECARBOXYLATE;(+)-n-boc-n,o-isopropylidene-d-serinal;(r)-(+)-3-boc-2,2-dimethyloxazolidine-4-carboxaldehyde
• CAS NO: 95715-87-0
• Molecular Formula: C₁₁H₁₉NO₄
• Molecular Weight: 229.27
• Product Categories: pharmacetical;Amiens;Heterocycles;Intermediates & Fine Chemicals;Pharmaceuticals
• Mol File: 95715-87-0.mol
• Article Data: 44

Chemical Properties

• Boiling Point: 67 °C/0.3 mmHg(lit.)
• Flash Point: 107 °C
• Appearance: Colorless to pale yellow/Oil
• Density: 1.06 g/mL at 25 °C(lit.)
• Vapor Pressure: 0.000972mmHg at 25°C
• Refractive Index: 1.445-1.447
• Storage Temp.: under inert gas (nitrogen or Argon) at 2-8°C
• Solubility: Chloroform, Dichloromethane, Ethyl Acetate
• PKA: -3.26±0.60(Predicted)
• Sensitive: Air Sensitive
• BRN: 3651554
• CAS DataBase Reference: TERT-BUTYL (R)-(+)-4-FORMYL-2,2-DIMETHYL-3-OXAZOLIDINECARBOXYLATE(CAS DataBase Reference)
• NIST Chemistry Reference: TERT-BUTYL (R)-(+)-4-FORMYL-2,2-DIMETHYL-3-OXAZOLIDINECARBOXYLATE(95715-87-0)
• EPA Substance Registry System: TERT-BUTYL (R)-(+)-4-FORMYL-2,2-DIMETHYL-3-OXAZOLIDINECARBOXYLATE(95715-87-0)

Safety Data

• Hazard Codes: Xi
• Statements: 36/37/38
• Safety Statements: 37/39-26-36-60-37-23
• WGK Germany: 3
• Hazardous Substances Data: 95715-87-0(Hazardous Substances Data)

Usage

Description

TERT-BUTYL (R)-(+)-4-FORMYL-2,2-DIMETHYL-3-OXAZOLIDINECARBOXYLATE is a chiral compound that serves as a key intermediate in the synthesis of various pharmaceuticals and bioactive molecules. Its unique structure, featuring a tert-butyl group, a formyl group, and a 2,2-dimethyl-3-oxazolidinecarboxylate moiety, makes it a versatile building block in organic chemistry.

Uses

Used in Pharmaceutical Industry:
TERT-BUTYL (R)-(+)-4-FORMYL-2,2-DIMETHYL-3-OXAZOLIDINECARBOXYLATE is used as a chiral building block for the synthesis of enantiomerically pure drugs and pharmaceuticals. Its unique structure allows for the creation of complex molecules with specific biological activities, making it a valuable tool in drug discovery and development.
Used in Organic Synthesis:
TERT-BUTYL (R)-(+)-4-FORMYL-2,2-DIMETHYL-3-OXAZOLIDINECARBOXYLATE is used as a versatile intermediate in organic synthesis for the preparation of various bioactive compounds. Its formyl group can be readily modified, allowing for the introduction of different functional groups and the formation of a wide range of target molecules.
Used in the Preparation of Fluorinated Analogs:
TERT-BUTYL (R)-(+)-4-FORMYL-2,2-DIMETHYL-3-OXAZOLIDINECARBOXYLATE is used in the preparation of fluorinated analogs of glutamic acid and glutamine. These analogs have potential applications in the development of new drugs and therapeutic agents, as well as in the study of metabolic pathways and enzyme mechanisms.

InChI:InChI=1/C11H19NO4/c1-10(2,3)16-9(14)12-8(6-13)7-15-11(12,4)5/h6,8H,7H2,1-5H3/t8-/m0/s1

Synthetic route

tert-butyl (4S)-4-(hydroxymethyl)-2,2-dimethyl-1,3-oxazolidine-3-carboxylate (108149-63-9, 108149-65-1) → (R)-3-tert-butoxycarbonyl-4-formyl-2,2-dimethyloxazolidine (95715-87-0)

Conditions	Yield
Stage #1: tert-butyl (4S)-4-(hydroxymethyl)-2,2-dimethyl-1,3-oxazolidine-3-carboxylate With oxalyl dichloride In dichloromethane; dimethyl sulfoxide at -60 - -45℃; for 0.666667h; Inert atmosphere; Stage #2: With triethylamine In dichloromethane; dimethyl sulfoxide at -45℃; Inert atmosphere;	100%
With Dess-Martin periodane In dichloromethane for 2h; Ambient temperature;	93%
With Dess-Martin periodane; 1-butyl-3-methylimidazolium Tetrafluoroborate at 20℃; for 4h; Dess-Martin oxidation;	90%

(R)-N,O-isopropylidenyl-2-(N-tert-butyloxycarbonylamino)-3-oxo-propanamide-N,O-dimethyl-hydroxyamine (167102-62-7) → (R)-3-tert-butoxycarbonyl-4-formyl-2,2-dimethyloxazolidine (95715-87-0)

Conditions	Yield
With lithium aluminium tetrahydride In tetrahydrofuran at 0℃; for 0.5h;	100%
With lithium aluminium tetrahydride In 2-methyltetrahydrofuran at 0℃;	100%
With lithium aluminium tetrahydride In tetrahydrofuran for 2.33333h; Inert atmosphere; Cooling;	92%
With sodium bis(2-methoxyethoxy)aluminium dihydride In toluene at 0 - 30℃; for 3h;	100 g

methyl [(4R)-3-(tert-butoxycarbonyl)-2,2-dimethyl-1,3-oxazolidin-4-yl]carboxylate (108149-60-6, 95715-86-9) → (R)-3-tert-butoxycarbonyl-4-formyl-2,2-dimethyloxazolidine (95715-87-0)

Conditions	Yield
With diisobutylaluminium hydride In toluene at -60 - 0℃; for 2.5h;	95%
With diisobutylaluminium hydride In toluene at -78 - -70℃; for 4h; Inert atmosphere;	89%
With diisobutylaluminium hydride In toluene at -78℃; for 2h;	85%

(4R)-3-(tert-butoxycarbonyl)-2,2-dimethyl-1,3-oxazolidine-4-carboxylic acid (660852-86-8) → (R)-3-tert-butoxycarbonyl-4-formyl-2,2-dimethyloxazolidine (95715-87-0)

Conditions	Yield
With oxalyl dichloride; dimethyl sulfoxide; triethylamine In dichloromethane at -78 - 0℃; for 2h; Swern Oxidation;	85%

2,2-dimethyl-oxazole-3-carboxylic acid tert-butyl ester + dicarbonylacetylacetonato rhodium (I) → (R)-3-tert-butoxycarbonyl-4-formyl-2,2-dimethyloxazolidine (95715-87-0) + tert-butyl 4-formyl-2,2-dimethyloxazolidine-3-carboxylate (95715-87-0, 102308-32-7, 144070-30-4, 127589-93-9)

Conditions	Yield
With 2,2',2'',2'''-(1,2-phenylenebis((1R,3R)-tetrahydro-5,8-dioxo-1H-(1,2,4)diazaphospholo(1,2-a)pyridazine-2,1,3(3H)-triyl))tetrakis(N-(1S)-1-phenylethyl)-benzamide In tetrahydrofuran at 55℃; under 7240.26 Torr; for 72h; Inert atmosphere; optical yield given as %ee; enantioselective reaction;	A 71% B n/a

(S)-2,2-dimethyl-oxazolidine-3,4-dicarboxylic acid 3-tert-butyl ester 4-methyl ester (95715-86-9, 108149-60-6) → (R)-3-tert-butoxycarbonyl-4-formyl-2,2-dimethyloxazolidine (95715-87-0)

Conditions	Yield
With diisobutylaluminium hydride In toluene at -80℃; for 4h; Automated synthesizer;	71%

D-Serine (312-84-5) + di-tert-butyl dicarbonate (24424-99-5) + 2,2-dimethoxy-propane (77-76-9) → (R)-3-tert-butoxycarbonyl-4-formyl-2,2-dimethyloxazolidine (95715-87-0)

Conditions	Yield
Multistep reaction;	51%

methyl [(4R)-3-(tert-butoxycarbonyl)-2,2-dimethyl-1,3-oxazolidin-4-yl]carboxylate (108149-60-6, 95715-86-9) → (R)-3-tert-butoxycarbonyl-4-formyl-2,2-dimethyloxazolidine (95715-87-0) + tert-butyl (4S)-4-(hydroxymethyl)-2,2-dimethyl-1,3-oxazolidine-3-carboxylate (108149-63-9, 108149-65-1)

Conditions	Yield
With diisobutylaluminium hydride In toluene at -78℃;	A 40% B 8%

1,1-dimethylethyl 4-(hydroxymethyl)-2,2-dimethyl-1,3-oxazolidine-3-carboxylate → (4S)-4-formyl-2,2-dimethyl-oxazolidine-3-carboxylic acid tert-butyl ester (102308-32-7) + (R)-3-tert-butoxycarbonyl-4-formyl-2,2-dimethyloxazolidine (95715-87-0)

Conditions	Yield
With oxalyl dichloride; dimethyl sulfoxide; triethylamine 1.) CH2Cl2, -78 deg C, 15 min, 2.) -78 deg C to r.t.; Yield given. Multistep reaction. Yields of byproduct given. Title compound not separated from byproducts;

(R)-4-(1,2-Dihydroxy-ethyl)-2,2-dimethyl-oxazolidine-3-carboxylic acid tert-butyl ester → (R)-3-tert-butoxycarbonyl-4-formyl-2,2-dimethyloxazolidine (95715-87-0)

Conditions	Yield
With sodium periodate; silica gel In dichloromethane Ambient temperature; Yield given;

D-Serine (312-84-5) + (CH3)2CX, (CH3)3CHOCOX → (R)-3-tert-butoxycarbonyl-4-formyl-2,2-dimethyloxazolidine (95715-87-0)

Conditions	Yield
Yield given. Multistep reaction;

(R)-N-tert-butoxycarbonyl serine (3262-72-4, 3850-40-6, 6368-20-3, 90582-28-8, 84311-18-2) → (R)-3-tert-butoxycarbonyl-4-formyl-2,2-dimethyloxazolidine (95715-87-0)

Conditions	Yield
Multi-step reaction with 3 steps 1: 86 percent / K2CO3 / dimethylformamide / 1.5 h / 0 - 20 °C 2: 80 percent / p-TsOH / benzene / 1 h / Heating 3: 75 percent / DIBAL-H / toluene / 2 h / -78 °C View Scheme
Multi-step reaction with 3 steps 1: N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride, N-methylmorpholine / CH2Cl2 / 1 h / -15 °C 2: BF3*Et2O / acetone / 1.5 h / Ambient temperature 3: 100 percent / LiAlH4 / tetrahydrofuran / 0.5 h / 0 °C View Scheme
Multi-step reaction with 3 steps 1: 0.5 h / 0 °C 2: 80 percent / TsOH*H2O / benzene / 0.5 h 3: 85 percent / diisobutylaluminum hydride (DIBAL) / toluene / 2 h / -78 °C View Scheme

2-(tert-butoxycarbonylamino)-3-hydroxypropionic acid methyl ester (95715-85-8) → (R)-3-tert-butoxycarbonyl-4-formyl-2,2-dimethyloxazolidine (95715-87-0)

Conditions	Yield
Multi-step reaction with 2 steps 1: 80 percent / p-TsOH / benzene / 1 h / Heating 2: 75 percent / DIBAL-H / toluene / 2 h / -78 °C View Scheme
Multi-step reaction with 3 steps 1: 75 percent / TsOH*H2O / benzene / Heating 2: 96 percent / NaBH4, LiCl / ethanol; tetrahydrofuran / 4 h / Ambient temperature 3: 1.) trifluoroacetic anhydride, DMSO, 2.) Et3N / 1.) CH2Cl2, -78 deg C, 1 h, 2.) CH2Cl2, from -78 deg C to 25 deg C View Scheme
Multi-step reaction with 2 steps 1: 80 percent / TsOH*H2O / benzene / 0.5 h 2: 85 percent / diisobutylaluminum hydride (DIBAL) / toluene / 2 h / -78 °C View Scheme

di-tert-butyl dicarbonate (24424-99-5) → (R)-3-tert-butoxycarbonyl-4-formyl-2,2-dimethyloxazolidine (95715-87-0)

Conditions	Yield
Multi-step reaction with 4 steps 1: NaOH / dioxane; H2O / 48 h / 0 - 20 °C 2: N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride, N-methylmorpholine / CH2Cl2 / 1 h / -15 °C 3: BF3*Et2O / acetone / 1.5 h / Ambient temperature 4: 100 percent / LiAlH4 / tetrahydrofuran / 0.5 h / 0 °C View Scheme
Multi-step reaction with 5 steps 1: 100 percent / Et3N / tetrahydrofuran / a) RT, 6 h, b) 50 deg C, 2 h 2: 98 percent / LiBH4 / tetrahydrofuran / 12 h / Ambient temperature 3: 98 percent / BF3*Et2O / acetone / 2 h / Ambient temperature 4: 95 percent / H2 / Pd/C / ethyl acetate / 24 h / Ambient temperature 5: 93 percent / Dess-Martin periodinane / CH2Cl2 / 2 h / Ambient temperature View Scheme
Multi-step reaction with 4 steps 1: 1 N NaOH / dioxane / 1.) 5 deg C, 30 min, 2.) RT, 3.5 h 2: 0.5 h / 0 °C 3: 80 percent / TsOH*H2O / benzene / 0.5 h 4: 85 percent / diisobutylaluminum hydride (DIBAL) / toluene / 2 h / -78 °C View Scheme

tert-butyl N-[(1R)-1-(hydroxymethyl)-2-[methoxy(methyl)amino]-2-oxo-ethyl]carbamate (167102-61-6) → (R)-3-tert-butoxycarbonyl-4-formyl-2,2-dimethyloxazolidine (95715-87-0)

Conditions	Yield
Multi-step reaction with 2 steps 1: BF3*Et2O / acetone / 1.5 h / Ambient temperature 2: 100 percent / LiAlH4 / tetrahydrofuran / 0.5 h / 0 °C View Scheme
Multi-step reaction with 2 steps 1: boron trifluoride diethyl etherate / 2 h / 20 °C 2: lithium aluminium tetrahydride / tetrahydrofuran / 2.33 h / Inert atmosphere; Cooling View Scheme
Multi-step reaction with 2 steps 1: boron trifluoride diethyl etherate / acetone / 0.05 h / 25 - 30 °C 2: sodium bis(2-methoxyethoxy)aluminium dihydride / toluene / 3 h / 0 - 30 °C View Scheme

N-(tert-butoxycarbonyl)-L-serine methyl ester (2766-43-0) → (R)-3-tert-butoxycarbonyl-4-formyl-2,2-dimethyloxazolidine (95715-87-0)

Conditions	Yield
Multi-step reaction with 5 steps 1: imidazole / CH2Cl2 / 12 h / Ambient temperature 2: LiBH4 / tetrahydrofuran / 12 h / Ambient temperature 3: 94 percent / BF3*Et2O / acetone / 2 h / Ambient temperature 4: 98 percent / Bu4NF / tetrahydrofuran / 2 h / Ambient temperature 5: 93 percent / Dess-Martin periodinane / CH2Cl2 / 2 h / Ambient temperature View Scheme
Multi-step reaction with 2 steps 1: 93 percent / BF3OEt2 / acetone / 12 h / Ambient temperature 2: 78 percent / DIBAL-H / toluene / 1.5 h / -78 °C View Scheme
Multi-step reaction with 5 steps 1.1: 1H-imidazole / dichloromethane / 0 - 20 °C 2.1: lithium aluminium tetrahydride / tetrahydrofuran / 1.5 h / 0 °C / Inert atmosphere 3.1: toluene-4-sulfonic acid / toluene / 1.5 h / Reflux; Inert atmosphere 4.1: tetrabutyl ammonium fluoride / tetrahydrofuran / 2 h / 0 - 20 °C 5.1: oxalyl dichloride; dimethyl sulfoxide / dichloromethane / 0.58 h / -78 °C 5.2: 0.08 h / -78 - 0 °C View Scheme
Multi-step reaction with 2 steps 1: boron trifluoride diethyl etherate / dichloromethane / 3 h / 25 °C / Automated synthesizer 2: diisobutylaluminium hydride / toluene / 4 h / -80 °C / Automated synthesizer View Scheme

(S)-tert-butyl (1-hydroxy-4-(methylthio)butan-2-yl)carbamate (51372-93-1) → (R)-3-tert-butoxycarbonyl-4-formyl-2,2-dimethyloxazolidine (95715-87-0)

Conditions	Yield
Multi-step reaction with 5 steps 1: 95 percent / BF3*Et2O / acetone / Ambient temperature 2: 93 percent / NaIO4, NaHCO3 / methanol; H2O / 0 °C 3: 69 percent / various solvent(s) / 6 h / 175 - 180 °C 4: OsO4, NMO / acetone / Ambient temperature 5: NaIO4, SiO2 / CH2Cl2 / Ambient temperature View Scheme

N-(tert-butyloxycarbonyl)-O-benzyl-L-serinol (79069-15-1) → (R)-3-tert-butoxycarbonyl-4-formyl-2,2-dimethyloxazolidine (95715-87-0)

Conditions	Yield
Multi-step reaction with 3 steps 1: 98 percent / BF3*Et2O / acetone / 2 h / Ambient temperature 2: 95 percent / H2 / Pd/C / ethyl acetate / 24 h / Ambient temperature 3: 93 percent / Dess-Martin periodinane / CH2Cl2 / 2 h / Ambient temperature View Scheme

methyl O-benzyl-N-(tert-butoxycarbonyl)-L-serinate (80963-10-6) → (R)-3-tert-butoxycarbonyl-4-formyl-2,2-dimethyloxazolidine (95715-87-0)

Conditions	Yield
Multi-step reaction with 4 steps 1: 98 percent / LiBH4 / tetrahydrofuran / 12 h / Ambient temperature 2: 98 percent / BF3*Et2O / acetone / 2 h / Ambient temperature 3: 95 percent / H2 / Pd/C / ethyl acetate / 24 h / Ambient temperature 4: 93 percent / Dess-Martin periodinane / CH2Cl2 / 2 h / Ambient temperature View Scheme

tert-butyl (4S)-2,2-dimethyl-4-vinyl-1,3-oxazolidine-3-carboxylate (133625-87-3) → (R)-3-tert-butoxycarbonyl-4-formyl-2,2-dimethyloxazolidine (95715-87-0)

Conditions	Yield
Multi-step reaction with 2 steps 1: OsO4, NMO / acetone / Ambient temperature 2: NaIO4, SiO2 / CH2Cl2 / Ambient temperature View Scheme

methyl (2S)-3-(2,2-dimethyl-1,1-diphenyl-1-silapropoxy)-2-[(tert-butoxy)carbonylamino]propanoate (159846-14-7) → (R)-3-tert-butoxycarbonyl-4-formyl-2,2-dimethyloxazolidine (95715-87-0)

Conditions	Yield
Multi-step reaction with 4 steps 1: LiBH4 / tetrahydrofuran / 12 h / Ambient temperature 2: 94 percent / BF3*Et2O / acetone / 2 h / Ambient temperature 3: 98 percent / Bu4NF / tetrahydrofuran / 2 h / Ambient temperature 4: 93 percent / Dess-Martin periodinane / CH2Cl2 / 2 h / Ambient temperature View Scheme

(S)-4-Benzyloxymethyl-2,2-dimethyl-oxazolidine-3-carboxylic acid tert-butyl ester (198417-68-4) → (R)-3-tert-butoxycarbonyl-4-formyl-2,2-dimethyloxazolidine (95715-87-0)

Conditions	Yield
Multi-step reaction with 2 steps 1: 95 percent / H2 / Pd/C / ethyl acetate / 24 h / Ambient temperature 2: 93 percent / Dess-Martin periodinane / CH2Cl2 / 2 h / Ambient temperature View Scheme

tert-butyl [(1R)-2-(tert-butyldiphenylsilyloxy)-1-(hydroxymethyl)-ethyl]carbamate (198417-69-5) → (R)-3-tert-butoxycarbonyl-4-formyl-2,2-dimethyloxazolidine (95715-87-0)

Conditions	Yield
Multi-step reaction with 3 steps 1: 94 percent / BF3*Et2O / acetone / 2 h / Ambient temperature 2: 98 percent / Bu4NF / tetrahydrofuran / 2 h / Ambient temperature 3: 93 percent / Dess-Martin periodinane / CH2Cl2 / 2 h / Ambient temperature View Scheme

(R)-4-(tert-Butyl-diphenyl-silanyloxymethyl)-2,2-dimethyl-oxazolidine-3-carboxylic acid tert-butyl ester (198417-70-8) → (R)-3-tert-butoxycarbonyl-4-formyl-2,2-dimethyloxazolidine (95715-87-0)

Conditions	Yield
Multi-step reaction with 2 steps 1: 98 percent / Bu4NF / tetrahydrofuran / 2 h / Ambient temperature 2: 93 percent / Dess-Martin periodinane / CH2Cl2 / 2 h / Ambient temperature View Scheme

(S)-2,2-Dimethyl-4-(2-methylsulfanyl-ethyl)-oxazolidine-3-carboxylic acid tert-butyl ester (197218-81-8) → (R)-3-tert-butoxycarbonyl-4-formyl-2,2-dimethyloxazolidine (95715-87-0)

Conditions	Yield
Multi-step reaction with 4 steps 1: 93 percent / NaIO4, NaHCO3 / methanol; H2O / 0 °C 2: 69 percent / various solvent(s) / 6 h / 175 - 180 °C 3: OsO4, NMO / acetone / Ambient temperature 4: NaIO4, SiO2 / CH2Cl2 / Ambient temperature View Scheme

(S)-4-(2-Methanesulfinyl-ethyl)-2,2-dimethyl-oxazolidine-3-carboxylic acid tert-butyl ester (197218-82-9) → (R)-3-tert-butoxycarbonyl-4-formyl-2,2-dimethyloxazolidine (95715-87-0)

Conditions	Yield
Multi-step reaction with 3 steps 1: 69 percent / various solvent(s) / 6 h / 175 - 180 °C 2: OsO4, NMO / acetone / Ambient temperature 3: NaIO4, SiO2 / CH2Cl2 / Ambient temperature View Scheme

2-(tert-Butoxycarbonyloxyimino)-2-phenylacetonitrile (58632-95-4) → (R)-3-tert-butoxycarbonyl-4-formyl-2,2-dimethyloxazolidine (95715-87-0)

Conditions	Yield
Multi-step reaction with 5 steps 1: Et3N / dioxane; H2O 2: methanol 3: CSA / acetone 4: LiAlH4 / diethyl ether / 0 °C 5: -78 °C / Swern ox. View Scheme

(S)-methyl 2-((tert-butoxycarbonyl)amino)-3-((tert-butyldimethylsilyl)oxy)propanoate (126645-26-9) → (R)-3-tert-butoxycarbonyl-4-formyl-2,2-dimethyloxazolidine (95715-87-0)

Conditions	Yield
Multi-step reaction with 4 steps 1.1: lithium aluminium tetrahydride / tetrahydrofuran / 1.5 h / 0 °C / Inert atmosphere 2.1: toluene-4-sulfonic acid / toluene / 1.5 h / Reflux; Inert atmosphere 3.1: tetrabutyl ammonium fluoride / tetrahydrofuran / 2 h / 0 - 20 °C 4.1: oxalyl dichloride; dimethyl sulfoxide / dichloromethane / 0.58 h / -78 °C 4.2: 0.08 h / -78 - 0 °C View Scheme

(R)-[1-(tert-butyl-dimethyl-silanyloxymethyl)-2-hydroxy-ethyl]-carbamic acid tert-butyl ester (152491-85-5) → (R)-3-tert-butoxycarbonyl-4-formyl-2,2-dimethyloxazolidine (95715-87-0)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: toluene-4-sulfonic acid / toluene / 1.5 h / Reflux; Inert atmosphere 2.1: tetrabutyl ammonium fluoride / tetrahydrofuran / 2 h / 0 - 20 °C 3.1: oxalyl dichloride; dimethyl sulfoxide / dichloromethane / 0.58 h / -78 °C 3.2: 0.08 h / -78 - 0 °C View Scheme

(R)-3-tert-butoxycarbonyl-4-formyl-2,2-dimethyloxazolidine (95715-87-0) → tert-butyl (4S)-4-(hydroxymethyl)-2,2-dimethyl-1,3-oxazolidine-3-carboxylate (108149-63-9, 108149-65-1)

Conditions	Yield
With zirconium(IV) tetraisopropoxide 2-propanol; 1,1'-bi-2-naphthol In toluene at 20℃; for 4h;	100%
With sodium tetrahydroborate In methanol at 0℃; for 1h;	84%
With zirconium(IV) tetraisopropoxide 2-propanol; 4 Angstroem MS; 1,1'-bi-2-naphthol In isopropyl alcohol; toluene at 20℃; for 12h;	70%
With sodium tetrahydroborate In tetrahydrofuran; isopropyl alcohol for 0.5h;	64%

(R)-3-tert-butoxycarbonyl-4-formyl-2,2-dimethyloxazolidine (95715-87-0) + allylmagnesium bromide (1730-25-2) → 1,1-dimethylethyl (4R)-(1'-hydroxy-3'-butenyl)-2,2-dimethyl-3-oxazolidinecarboxylate (220317-60-2)

Conditions	Yield
	100%

(R)-3-tert-butoxycarbonyl-4-formyl-2,2-dimethyloxazolidine (95715-87-0) + (carbethoxyethylidene)triphenylphosphorane (21382-82-1) → ethyl 2-methyl-3-[3-(tert-butoxycarbonyl)-2,2-dimethyl-(4S)-oxazolidinyl]prop-(2E)-enoate (916912-39-5)

Conditions	Yield
In dichloromethane at 20℃; for 12h;	100%
In benzene Wittig reaction; Reflux;	84%
In dichloromethane at 20℃;

O-methylresorcine (150-19-6) + (R)-3-tert-butoxycarbonyl-4-formyl-2,2-dimethyloxazolidine (95715-87-0) → tert-butyl (R)-4-((R)-hydroxy(2-hydroxy-4-methoxyphenyl)methyl)-2,2-dimethyloxazolidine-3-carboxylate (925703-63-5)

Conditions	Yield
Stage #1: O-methylresorcine With methylmagnesium chloride In tetrahydrofuran at 20℃; for 0.166667h; Stage #2: (R)-3-tert-butoxycarbonyl-4-formyl-2,2-dimethyloxazolidine In dichloromethane at 0 - 20℃; for 15h;	100%

C27H31N5O6S*2ClH + (R)-3-tert-butoxycarbonyl-4-formyl-2,2-dimethyloxazolidine (95715-87-0) → C38H50N6O9S (1111235-29-0)

Conditions	Yield
Stage #1: C27H31N5O6S*2ClH; (R)-3-tert-butoxycarbonyl-4-formyl-2,2-dimethyloxazolidine With sodium tris(acetoxy)borohydride; triethylamine In dichloromethane at 20℃; for 16h; Stage #2: With water; potassium carbonate In dichloromethane at 20℃;	100%

1-ethynyl-4-(n-pentyl)benzene (79887-10-8) + (R)-3-tert-butoxycarbonyl-4-formyl-2,2-dimethyloxazolidine (95715-87-0) → C24H35NO4 (1207432-32-3)

Conditions	Yield
Stage #1: 1-ethynyl-4-(n-pentyl)benzene With n-butyllithium In tetrahydrofuran; hexane at -20℃; for 2h; Inert atmosphere; Stage #2: With N,N,N,N,N,N-hexamethylphosphoric triamide In tetrahydrofuran; hexane at -78℃; for 0.5h; Inert atmosphere; Stage #3: (R)-3-tert-butoxycarbonyl-4-formyl-2,2-dimethyloxazolidine In tetrahydrofuran; hexane at -78 - -60℃; for 5h; Inert atmosphere;	100%

Sesamol (533-31-3) + (R)-3-tert-butoxycarbonyl-4-formyl-2,2-dimethyloxazolidine (95715-87-0) → tert-butyl (R)-4-((R)-hydroxy(6-hydroxybenzo[d][1,3]dioxol-5-yl)methyl)-2,2-dimethyloxazolidine-3-carboxylate (925703-84-0)

Conditions	Yield
Stage #1: Sesamol With methylmagnesium chloride In tetrahydrofuran at 20℃; for 0.166667h; Stage #2: (R)-3-tert-butoxycarbonyl-4-formyl-2,2-dimethyloxazolidine In dichloromethane at 0 - 20℃; for 15h;	99%

diazoacetic acid ethyl ester (623-73-4) + (R)-3-tert-butoxycarbonyl-4-formyl-2,2-dimethyloxazolidine (95715-87-0) → (2E',4S)-4-(2'-ethoxycarbonyl-vinyl)-2,2-dimethyl-oxazolidine-3-carboxylic acid tert-butyl ester (134525-18-1, 131713-27-4, 144070-31-5, 149406-02-0)

Conditions	Yield
With Fe(TCP)Cl; polyethylene supported arsine; polymethylhydrosiloxane In toluene at 110℃; for 12h; Wittig type reaction; Inert atmosphere; stereoselective reaction;	99%

(R)-3-tert-butoxycarbonyl-4-formyl-2,2-dimethyloxazolidine (95715-87-0) + 4-methylbenzo[1,3]dioxol-5-ol (187040-03-5) → (R)-4-[(R)-Hydroxy-(6-hydroxy-7-methyl-benzo[1,3]dioxol-5-yl)-methyl]-2,2-dimethyl-oxazolidine-3-carboxylic acid tert-butyl ester (654643-98-8)

Conditions	Yield
With methylmagnesium chloride In tetrahydrofuran; dichloromethane at 20℃;	98%
Stage #1: 4-methylbenzo[1,3]dioxol-5-ol With methylmagnesium chloride In tetrahydrofuran Stage #2: (R)-3-tert-butoxycarbonyl-4-formyl-2,2-dimethyloxazolidine In dichloromethane Further stages.;	98%
Stage #1: 4-methylbenzo[1,3]dioxol-5-ol With methylmagnesium chloride In tetrahydrofuran; hexane at 20℃; for 0.5h; Stage #2: (R)-3-tert-butoxycarbonyl-4-formyl-2,2-dimethyloxazolidine In tetrahydrofuran; hexane; dichloromethane at 20℃;	98%

3-bromo-3,3-difluropropene (420-90-6) + (R)-3-tert-butoxycarbonyl-4-formyl-2,2-dimethyloxazolidine (95715-87-0) → C14H23F2NO4 (1056467-63-0)

Conditions	Yield
With indium; lithium iodide In N,N-dimethyl-formamide	98%

(R)-3-tert-butoxycarbonyl-4-formyl-2,2-dimethyloxazolidine (95715-87-0) + (cyclopropylmethyl)triphenylphosphonium bromide (14799-82-7) → (S)-tert-butyl 4-(2-cyclopropylvinyl)-2,2-dimethyloxazolidine-3-carboxylate (1222186-28-8)

Conditions	Yield
Stage #1: (cyclopropylmethyl)triphenylphosphonium bromide With potassium hexamethylsilazane In tetrahydrofuran at -78 - 20℃; for 1h; Stage #2: (R)-3-tert-butoxycarbonyl-4-formyl-2,2-dimethyloxazolidine In tetrahydrofuran at -78℃;	96%

(R)-3-tert-butoxycarbonyl-4-formyl-2,2-dimethyloxazolidine (95715-87-0) + methyl (triphenylphosphoranylidene)acetate (21204-67-1) → (4S)-1,1-Dimethylethyl 4-<(E)-3'-methoxy-3'-oxo-1'-propenyl>-2,2-dimethyl-3-oxazolidinecarboxylate (129483-65-4)

Conditions	Yield
In benzene Ambient temperature;	95%
In toluene at 0 - 20℃; for 40h;	77%

(R)-3-tert-butoxycarbonyl-4-formyl-2,2-dimethyloxazolidine (95715-87-0) + ethylamine (75-04-7) → (S)-4-ethylaminomethyl-2,2-dimethyl-oxazolidine-3-carboxylic acid tert-butyl ester (1048351-33-2)

Conditions	Yield
Stage #1: (R)-3-tert-butoxycarbonyl-4-formyl-2,2-dimethyloxazolidine; ethylamine In methanol at 20℃; for 1.5h; Molecular sieve; Stage #2: With hydrogen; palladium on activated charcoal In methanol at 20℃; under 760.051 Torr;	95%

cycl-isopropylidene malonate (2033-24-1) + (R)-3-tert-butoxycarbonyl-4-formyl-2,2-dimethyloxazolidine (95715-87-0) → (4S)-4-(2,2-dimethyl-4,6-dioxo-[1,3]dioxan-5-ylmethyl)-2,2-dimethyl-oxazolidine-3-carboxylic acid tert-butyl ester

Conditions	Yield
With diethyl 2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate; L-proline In acetonitrile at 25℃;	95%

(R)-3-tert-butoxycarbonyl-4-formyl-2,2-dimethyloxazolidine (95715-87-0) + N-ε-(2-Chloro-CBZ)-L-lysine allyl ester hydrochloride (144156-17-2) → (S)-4-{[(S)-1-Allyloxycarbonyl-5-(2-chloro-benzyloxycarbonylamino)-pentylamino]-methyl}-2,2-dimethyl-oxazolidine-3-carboxylic acid tert-butyl ester (144156-07-0)

Conditions	Yield
With sodium cyanoborohydride In methanol for 1h; Ambient temperature;	94%

3-bromofurane (22037-28-1) + (R)-3-tert-butoxycarbonyl-4-formyl-2,2-dimethyloxazolidine (95715-87-0) → C15H23NO5 (1105713-64-1)

Conditions	Yield
With n-butyllithium In tetrahydrofuran at -78℃;	93%

(R)-3-tert-butoxycarbonyl-4-formyl-2,2-dimethyloxazolidine (95715-87-0) + sodium chlorodifluoroacetate (1895-39-2) → C12H19F2NO3

Conditions	Yield
With triphenylphosphine In N,N-dimethyl-formamide at 100℃; for 2h; Inert atmosphere;	92.31%

carbon tetrabromide (558-13-4) + (R)-3-tert-butoxycarbonyl-4-formyl-2,2-dimethyloxazolidine (95715-87-0) → (S)-tert-butyl 4-(2,2-dibromovinyl)-2,2-dimethyloxazolidine-3-carboxylate (130418-98-3)

Conditions	Yield
With triphenylphosphine In dichloromethane at 0 - 20℃; for 2.33333h;	92%
Stage #1: carbon tetrabromide With triphenylphosphine In dichloromethane at -30℃; for 0.666667h; Inert atmosphere; Stage #2: (R)-3-tert-butoxycarbonyl-4-formyl-2,2-dimethyloxazolidine With triethylamine In dichloromethane at -60 - 0℃; for 2.5h; Inert atmosphere; Stage #3: With sodium hydrogencarbonate In dichloromethane; water	88%
With triphenylphosphine	72%
With triethylamine; triphenylphosphine 1.) CH2Cl2, -20 deg C, 30 min; 2.) CH2Cl2, -60 deg C, 30 min, r.t., overnight; Multistep reaction;
With triethylamine; triphenylphosphine 1) CH2Cl2, -20 deg C, 30 min; 2) CH2Cl2, -60 deg C, 30 min, rt, overnight; Yield given. Multistep reaction;

vinyl magnesium bromide (1826-67-1) + (R)-3-tert-butoxycarbonyl-4-formyl-2,2-dimethyloxazolidine (95715-87-0) → (4R)-4-(1-hydroxy-allyl)-2,2-dimethyl-oxazolidine-3-carboxylic acid tert-butyl ester (768387-35-5)

Conditions	Yield
at -78 - -20℃; for 1.5h;	92%
Addition;	81%
In tetrahydrofuran -78 deg C -> -50 deg C, 2 h;	74%

2,2,4,4-Tetrakis(trifluoromethyl)-1,3-dithietane (791-50-4) + (R)-3-tert-butoxycarbonyl-4-formyl-2,2-dimethyloxazolidine (95715-87-0) → 2,2-dimethyl-4-(3,3,3-trifluoro-2-trifluoromethyl-propenyl)-oxazolidine-3-carboxylic acid tert-butyl ester (340714-52-5)

Conditions	Yield
With triphenylphosphine In diethyl ether at -78 - 20℃; for 72h; Wittig reaction;	92%
With triphenylphosphine In diethyl ether at -78 - 20℃; for 72h;	92%

tetravinyltin (IV) (1112-56-7) + (R)-3-tert-butoxycarbonyl-4-formyl-2,2-dimethyloxazolidine (95715-87-0) → (1'R,4R)-3-(tert-butoxycarbonyl)-2,2-dimethyl-4-(1-hydroxy-2-propen-1-yl)-1,3-oxazolidine (114301-35-8) + (4R,1'S)-4-(1-hydroxy-allyl)-2,2-dimethyl-oxazolidine-3-carboxylic acid tert-butyl ester (114301-34-7)

Conditions	Yield
Stage #1: tetravinyltin (IV) With methyllithium In diethyl ether at 0℃; for 0.25h; Inert atmosphere; Stage #2: With zinc dibromide In diethyl ether at 20℃; for 1h; Inert atmosphere; Stage #3: (R)-3-tert-butoxycarbonyl-4-formyl-2,2-dimethyloxazolidine In diethyl ether at -35 - 20℃; Inert atmosphere;	A 92% B n/a
Stage #1: tetravinyltin (IV) With methyllithium; zinc dibromide In diethyl ether at 20℃; for 1h; Stage #2: (R)-3-tert-butoxycarbonyl-4-formyl-2,2-dimethyloxazolidine In diethyl ether at 20℃; for 2h; Title compound not separated from byproducts;
Stage #1: tetravinyltin (IV) With methyllithium In diethyl ether at 0℃; for 0.25h; Stage #2: With zinc dibromide In diethyl ether at 20℃; for 1h; Stage #3: (R)-3-tert-butoxycarbonyl-4-formyl-2,2-dimethyloxazolidine With zinc dibromide In diethyl ether at -78 - 20℃; Title compound not separated from byproducts;

(R)-3-tert-butoxycarbonyl-4-formyl-2,2-dimethyloxazolidine (95715-87-0) + (bromomethyl)pentafluorobenzene (1765-40-8) → (S)-2,2-Dimethyl-4-((E)-2-pentafluorophenyl-vinyl)-oxazolidine-3-carboxylic acid tert-butyl ester (752244-60-3)

Conditions	Yield
Stage #1: (bromomethyl)pentafluorobenzene With triphenylphosphine In tetrahydrofuran for 0.25h; Stage #2: With potassium tert-butylate In tetrahydrofuran at 0℃; for 1.5h; Wittig olefination; Stage #3: (R)-3-tert-butoxycarbonyl-4-formyl-2,2-dimethyloxazolidine In tetrahydrofuran at -78 - 20℃; for 14h; Wittig olefination;	92%

methylmagnesium bromide (75-16-1) + (R)-3-tert-butoxycarbonyl-4-formyl-2,2-dimethyloxazolidine (95715-87-0) → (4R)-(1-hydroxy-ethyl)-2,2-dimethyl-oxazolidine-3-carboxylic acid tert-butyl ester (488727-69-1)

Conditions	Yield
In tetrahydrofuran; diethyl ether at 20℃; for 3h;	91%
In tetrahydrofuran at -78 - 25℃; Inert atmosphere;	77%

tetravinyltin (IV) (1112-56-7) + (R)-3-tert-butoxycarbonyl-4-formyl-2,2-dimethyloxazolidine (95715-87-0) → (4R)-4-(1-hydroxy-allyl)-2,2-dimethyl-oxazolidine-3-carboxylic acid tert-butyl ester (768387-35-5)

Conditions	Yield
With N,N,N,N,N,N-hexamethylphosphoric triamide; methyllithium In diethyl ether at -78℃; for 2h;	91%

3,4-dimethoxyphenol (2033-89-8) + (R)-3-tert-butoxycarbonyl-4-formyl-2,2-dimethyloxazolidine (95715-87-0) → tert-butyl (R)-4-((R)-hydroxy(2-hydroxy-4,5-dimethoxyphenyl)methyl)-2,2-dimethyloxazolidine-3-carboxylate (925703-87-3)

Conditions	Yield
Stage #1: 3,4-dimethoxyphenol With methylmagnesium chloride In tetrahydrofuran at 20℃; for 0.166667h; Stage #2: (R)-3-tert-butoxycarbonyl-4-formyl-2,2-dimethyloxazolidine In dichloromethane at 0 - 20℃; for 15h;	91%

(R)-3-tert-butoxycarbonyl-4-formyl-2,2-dimethyloxazolidine (95715-87-0) + 3-chloro-aniline (108-42-9) → (S)-4-[(3-chlorophenylamino)methyl]-2,2-dimethyloxazolidine-3-carboxylic acid tert-butyl ester (1048351-01-4)

Conditions	Yield
With sodium cyanoborohydride; zinc(II) chloride In methanol at 20 - 40℃; for 3h; Inert atmosphere;	91%

(R)-3-tert-butoxycarbonyl-4-formyl-2,2-dimethyloxazolidine (95715-87-0) + ethyl (triphenylphosphoranylidene)acetate (1099-45-2) → (2E',4S)-4-(2'-ethoxycarbonyl-vinyl)-2,2-dimethyl-oxazolidine-3-carboxylic acid tert-butyl ester (134525-18-1, 131713-27-4, 144070-31-5, 149406-02-0)

Conditions	Yield
In tetrahydrofuran for 2.5h; Heating;	90%
In benzene at 20℃; for 36h;	85%
In tetrahydrofuran at 25℃; for 12h; Condensation;	72%

Upstream product

• 108149-63-9 tert-butyl (4S)-4-(hydroxymethyl)-2,2-dimethyl-1,3-oxazolidine-3-carboxylate 
• 80963-10-6 methyl O-benzyl-N-(tert-butoxycarbonyl)-L-serinate 
• 197218-82-9 (S)-4-(2-Methanesulfinyl-ethyl)-2,2-dimethyl-oxazolidine-3-carboxylic acid tert-butyl ester 
• 108149-63-9 4-hydroxymethyl-2,2-dimethyloxazolidine-3-carboxylic acid tert-butyl ester 
• 69942-12-7 N-tert-butoxycarbonylserine methyl ester 
• 24424-99-5 di-tert-butyl dicarbonate 
• 157604-46-1 3-tert-butyl 4-methyl 2,2-dimethyl-1,3-oxazolidine-3,4-dicarboxylate 
• 95715-86-9 (S)-2,2-dimethyl-oxazolidine-3,4-dicarboxylic acid 3-tert-butyl ester 4-methyl ester 
• 660852-86-8 (4R)-3-(tert-butoxycarbonyl)-2,2-dimethyl-1,3-oxazolidine-4-carboxylic acid 
• 108149-60-6 methyl [(4R)-3-(tert-butoxycarbonyl)-2,2-dimethyl-1,3-oxazolidin-4-yl]carboxylate 
• 83345-44-2 3-tert-butoxycarbonylamino-4-hydroxy-butyric acid 
• 136703-59-8 (3S)-3-[(tert-butoxycarbonyl)amino]-4-hydroxybutanoic acid methyl ester 
• 518986-07-7 (4S)-4-[(t-butyldimethylsilyloxy)methyl]-2,2-dimethyl-3-[(1,1-dimethylethoxy)carbonyl]oxazolidine 
• 152491-85-5 (R)-[1-(tert-butyl-dimethyl-silanyloxymethyl)-2-hydroxy-ethyl]-carbamic acid tert-butyl ester 

Downstream Products

• 129483-74-5 4-(1-Methoxycarbonylmethyl-2-phenyl-ethyl)-2,2-dimethyl-oxazolidine-3-carboxylic acid tert-butyl ester 
• 129483-67-6 (E)-4-tert-Butoxycarbonylamino-5-(3,3,3-trifluoro-2-methoxy-2-phenyl-propionyloxy)-pent-2-enoic acid methyl ester 
• 129483-74-5 4-(1-Methoxycarbonylmethyl-2-phenyl-ethyl)-2,2-dimethyl-oxazolidine-3-carboxylic acid tert-butyl ester 
• 129483-67-6 (E)-4-tert-Butoxycarbonylamino-5-(3,3,3-trifluoro-2-methoxy-2-phenyl-propionyloxy)-pent-2-enoic acid methyl ester 
• 127997-06-2 6,7-N,O-Isopropylidene-6-<(tert-butoxycarbonyl)amino>-2,3,6-trideoxy-D-ribo-hept-2-enono-1,4-lactone 
• 127997-05-1 6,7-N,O-Isopropylidene-6-<(tert-butoxycarbonyl)amino>-2,3,6-trideoxy-D-arabino-hept-2-enono-1,4-lactone 
• 133625-87-3 tert-butyl (4S)-2,2-dimethyl-4-vinyl-1,3-oxazolidine-3-carboxylate 
• 116079-35-7 tert-butyl (R)-4-((R)-hydroxy(2-hydroxy-5-tert-butylphenyl)methyl)-2,2-dimethyloxazolidine-3-carboxylate 
• 116079-45-9 (R)-4-[(R)-(2,6-Dihydroxy-4-pentadecyl-phenyl)-hydroxy-methyl]-2,2-dimethyl-oxazolidine-3-carboxylic acid tert-butyl ester 
• 116079-46-0 (R)-4-[(S)-(2,6-Dihydroxy-4-pentadecyl-phenyl)-hydroxy-methyl]-2,2-dimethyl-oxazolidine-3-carboxylic acid tert-butyl ester 
• 132639-35-1 tert-butyl (Z)-2,2-dimethyl-4-(2'-phenylvinyl)-3-oxazolidinecarboxylate 
• 132639-34-0 tert-Butyl (E,4S)-2,2-dimethyl-4-(2'-phenylvinyl)-3-oxazolidine-3-carboxylate 
• 138372-01-7 1-Benzenesulfonyl-2-[1,3]dioxolan-2-yl-1H-pyrrole 
• 138372-16-4 t-Butyl (R)-4-<5-(1,3-dioxolan-2-yl)-1-(phenylsulfonyl)pyrrol-3-yl>hydroxymethyl-2,2-dimethyl-3-oxazolidinecarboxylate 

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PYRROLE COMPOUNDS

Provided herein are compounds of Formula (I), or pharmaceutically acceptable salts thereof, pharmaceutical compositions that include a compound described herein (including pharmaceutically acceptable salts of a compound described herein) and methods of synthesizing the same. Also provided herein are methods of treating diseases and/or conditions with a compound of Formula (I), or a pharmaceutically acceptable salt thereof.

STABLE N-((1R,2R)-1-(2,3-DIHYDROBENZO[B][1,4]DIOXIN-6-YL)-1-HYDROXY-3-(PYRROLIDIN-1-YL)PROPAN-2-YL) OCTANAMIDE (2R,3R)-2,3-DIHYDROXYSUCCINATE PREMIX AND PROCESS FOR PREPARATION THEREOF

The present invention related to stable N-((1R, 2R)-1-(2,3-dihydrobenzo[b][1,4] dioxin-6-yl)- 1-hydroxy-3- (pyrrolidin-1-yl)propan-2-yl) octanamide (2R,3R)- 2,3-dihydroxysuccinate premix of formula (Ia) and its process for preparation thereof. The present invention also related to process for the preparation of N-((1R, 2R)-1-(2,3-dihydrobenzo[b][1,4] dioxin-6- yl)-1-hydroxy-3- (pyrrolidin-1-yl) propan-2-yl) octanamide of formula (I) and pharmaceutically acceptable salts.