396731-40-1

Basic information

• Product Name: 3,5-Dioxo-piperidine-1-carboxylicacidtert-butylester
• Synonyms: 3,5-Dioxo-piperidine-1-carboxylicacidtert-butylester;1-Piperidinecarboxylic acid, 3,5-dioxo-, 1,1-diMethylethyl ester
• CAS NO: 396731-40-1
• Molecular Formula: C₁₀H₁₅NO₄
• Molecular Weight: 213.2304
• Mol File: 396731-40-1.mol
• Article Data: 1

Chemical Properties

• Boiling Point: 346.2±32.0 °C(Predicted)
• Appearance: /
• Density: 1.199±0.06 g/cm3(Predicted)
• Storage Temp.: under inert gas (nitrogen or Argon) at 2-8°C
• PKA: 9.72±0.20(Predicted)
• CAS DataBase Reference: 3,5-Dioxo-piperidine-1-carboxylicacidtert-butylester(CAS DataBase Reference)
• NIST Chemistry Reference: 3,5-Dioxo-piperidine-1-carboxylicacidtert-butylester(396731-40-1)
• EPA Substance Registry System: 3,5-Dioxo-piperidine-1-carboxylicacidtert-butylester(396731-40-1)

Safety Data

• Hazardous Substances Data: 396731-40-1(Hazardous Substances Data)

Usage

Description

3,5-Dioxo-piperidine-1-carboxylicacidtert-butylester is an organic compound that serves as a versatile intermediate in the synthesis of various pharmaceuticals and chemicals. It is characterized by its structural formula, which includes a piperidine ring with two oxygen atoms at the 3rd and 5th positions, and a tert-butylester group attached to the carboxylic acid.

Uses

Used in Organic Synthesis:
3,5-Dioxo-piperidine-1-carboxylicacidtert-butylester is used as an organic synthesis intermediate for the production of various chemical compounds. Its unique structure allows for further functionalization and modification, making it a valuable building block in the synthesis of complex organic molecules.
Used in Pharmaceutical Industry:
3,5-Dioxo-piperidine-1-carboxylicacidtert-butylester is used as a pharmaceutical intermediate, playing a crucial role in the development of new drugs and therapeutic agents. Its incorporation into drug molecules can enhance their pharmacological properties, such as potency, selectivity, and bioavailability.
Used in Laboratory Research and Development:
3,5-Dioxo-piperidine-1-carboxylicacidtert-butylester is utilized in the laboratory research and development process, where it is employed to study the synthesis, properties, and potential applications of novel chemical and pharmaceutical compounds. Its use in research helps to advance the understanding of its potential uses and to develop new methods for its synthesis and application.
Used in Chemical Production Process:
3,5-Dioxo-piperidine-1-carboxylicacidtert-butylester is also used in the chemical production process, where it is transformed into various end products through a series of chemical reactions. Its versatility as an intermediate allows for the production of a wide range of chemicals and pharmaceuticals, contributing to the diversity of products available in the market.

Synthesis

To a cooled (5 °C) and stirred mixture of potassium 2-methyl-2-propoxide (29.7 g,0.27 mol) was added a solution of ethyl [A/-((1,1-dimethylethoxy)carbonyl),A/-(2-oxopropyl)]glycinate (65 g, 0.25 mol) in ethyl ether (200 ml) over a period of 1.5 h. The re- sulting mixture was stirred for an additional 3 h, and the formed precipitate was filtered offand washed with ethyl ether (2 x 100 ml). The solid was dissolved in water (150 ml), andacetic acid was added to adjust the pH to 4. The product was filtered, washed with water (2x 50 ml) and air dried to furnish 1 -[(1,1 -dimethylethoxy)carbonyl]-3,5-dioxopiperidine (28 g,52 %).>xxN'TOHPLC-MS: m/z: 158 (M+H-56).1H-NMR (DMSO-d6): 81.48 (9H, s), 4.03 (4H, s), 5.38 (1 H, s).

Synthetic route

ethyl 2-(tert-butoxycarbonyl(2-oxopropyl)amino)acetate (873190-14-8) → tert-butyl 3,5-dioxopiperidine- 1-carboxylate (396731-40-1)

Conditions	Yield
With potassium tert-butylate In diethyl ether at 5℃; for 4.5h;	52%

tert-butyl 3,5-dioxopiperidine- 1-carboxylate (396731-40-1) → tert-butyl 4-bromo-3,5-dioxopiperidine-1-carboxylate (478624-67-8)

Conditions	Yield
With N-Bromosuccinimide; 2,2'-azobis(isobutyronitrile) In tetrachloromethane at 10 - 15℃; for 1.5h;	100%
With N-Bromosuccinimide; 1,1'-azobis(1-cyanocyclohexanenitrile) In dichloromethane at 0℃; for 2h; Inert atmosphere;	100%
With N-Bromosuccinimide; 1,1'-azobis(1-cyanocyclohexanenitrile) In dichloromethane at 0℃; for 2h; Inert atmosphere;	100%

tert-butyl 3,5-dioxopiperidine- 1-carboxylate (396731-40-1) + toluene-4-sulfonic acid hydrazide (1576-35-8) → tert-butyl 5-[(4-methylphenyl)hydrazinesulfonyl]-3-oxo-1,2,3,6-tetrahydropyridine-1-carboxylate

Conditions	Yield
With acetic acid In water at 0 - 25℃; for 48h; Inert atmosphere;	75%

tert-butyl 3,5-dioxopiperidine- 1-carboxylate (396731-40-1) + p-carboxybenzenesulfonyl azide (17202-49-2) → 1,1-dimethylethyl 4-azo-3,5-dioxo-1-piperidinecarboxylate

Conditions	Yield
With triethylamine In acetonitrile at 0 - 20℃; for 1.16667h;	72.3%

tert-butyl 3,5-dioxopiperidine- 1-carboxylate (396731-40-1) + phenyl isothiocyanate (103-72-0) → tert-butyl 5-hydroxy-3-oxo-4-(phenylcarbamothioyl)-3,6-dihydropyridine-1(2H)-carboxylate

Conditions	Yield
With 1,8-diazabicyclo[5.4.0]undec-7-ene In acetonitrile at 0 - 20℃; for 16h;	54%

3-nitro-4-pyridinecarboxaldehyde (153813-70-8) + tert-butyl 3,5-dioxopiperidine- 1-carboxylate (396731-40-1) → tert-butyl 4-oxo-1,3,5,10-tetrahydropyrido[3,4-b][1,7]naphthyridine-2-carboxylate

Conditions	Yield
With iron; acetic acid at 50℃; for 3h;	40%

tert-butyl 3,5-dioxopiperidine- 1-carboxylate (396731-40-1) + 2-nitro-benzaldehyde (552-89-6) → tert-butyl 4-oxo-1,3-dihydrobenzo[b][1,7]naphthyridine-2-carboxylate

Conditions	Yield
With iron; acetic acid at 50℃; for 1h;	37%

tert-butyl 3,5-dioxopiperidine- 1-carboxylate (396731-40-1) + 3-aminopyrazole (1820-80-0) + 3-(4-chlorophenoxy)benzaldehyde (69770-20-3) + trifluoroacetic acid (76-05-1) → 4-[3-(4-chlorophenoxy)phenyl]-2,4,6,7,8,9-hexahydropyrazolo[3,4-9b]-1,7-naphthyridin-5-one trifluoroacetic acid

Conditions	Yield
Stage #1: tert-butyl 3,5-dioxopiperidine- 1-carboxylate; 3-aminopyrazole; 3-(4-chlorophenoxy)benzaldehyde In ethanol for 0.5h; Reflux; Stage #2: trifluoroacetic acid In dichloromethane at 20℃; for 1h;	31%

tert-butyl 3,5-dioxopiperidine- 1-carboxylate (396731-40-1) + acetic anhydride (108-24-7) → C12H17NO5

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In dichloromethane at 22℃; for 17h;	28%

tert-butyl 3,5-dioxopiperidine- 1-carboxylate (396731-40-1) + 1-isothiocyanato-4-methylbenzene (622-59-3) → tert-butyl 5-hydroxy-4-[(4-methylphenyl)carbamothioyl]-3-oxo-3,6-dihydropyridine-1(2H)-carboxylate

Conditions	Yield
With 1,8-diazabicyclo[5.4.0]undec-7-ene In acetonitrile at 20℃; for 16h;	26%

tert-butyl 3,5-dioxopiperidine- 1-carboxylate (396731-40-1) + (4-fluorobenzyl)magnesium chloride (1643-73-8) → tert-butyl 3-(4-fluorobenzyl)-3-hydroxy-5-oxopiperidine-1-carboxylate

Conditions	Yield
Stage #1: tert-butyl 3,5-dioxopiperidine- 1-carboxylate With sodium hydride In tetrahydrofuran; mineral oil for 0.5h; Inert atmosphere; Stage #2: (4-fluorobenzyl)magnesium chloride In tetrahydrofuran; mineral oil at 20 - 60℃; for 4h;	25%

tert-butyl 3,5-dioxopiperidine- 1-carboxylate (396731-40-1) + 4-fluorophenyl isothiocyanate (1544-68-9) → tert-butyl 4-[(4-fluorophenyl)carbamothioyl]-5-hydroxy-3-oxo-3,6-dihydropyridine-1(2H)-carboxylate

Conditions	Yield
With 1,8-diazabicyclo[5.4.0]undec-7-ene In acetonitrile at 20℃; for 16h;	24%

2-pyridylisothiocyanate (52648-45-0) + tert-butyl 3,5-dioxopiperidine- 1-carboxylate (396731-40-1) → tert-butyl 5-hydroxy-3-oxo-4-(pyridin-2-ylcarbamothioyl)-3,6-dihydropyridine-1(2H)-carboxylate

Conditions	Yield
With 1,8-diazabicyclo[5.4.0]undec-7-ene In acetonitrile at 0 - 20℃; for 16h;	10%

tert-butyl 3,5-dioxopiperidine- 1-carboxylate (396731-40-1) + N,N-dimethyl-formamide dimethyl acetal (4637-24-5) → tert-butyl 4-((dimethylamino)methylene)-3,5-dioxopiperidine-1-carboxylate (478623-90-4)

Conditions	Yield
at 20 - 80℃; for 3.5h;
In toluene at 50 - 80℃; for 4h;

2-chloroethanal (107-20-0) + tert-butyl 3,5-dioxopiperidine- 1-carboxylate (396731-40-1) → 1,1-dimethylethyl 2-hydroxy-2,3,4,7-tetrahydro-4-oxo-furo[2,3-c]pyridine-6(5H)-carboxylate (478625-45-5)

Conditions	Yield
Stage #1: 2-chloroethanal; tert-butyl 3,5-dioxopiperidine- 1-carboxylate With sodium hydrogencarbonate In tetrahydrofuran; water at 0 - 20℃; Stage #2: With hydrogenchloride In tetrahydrofuran; water

tert-butyl 3,5-dioxopiperidine- 1-carboxylate (396731-40-1) + 3-aminopyrazole (1820-80-0) + trifluoroacetic acid (76-05-1) + 5-((1H-benzo[d]imidazol-2-yl)thio)furan-2-carbaldehyde (39689-08-2) → 4-[5-(1H-benzimidazol-2-ylsulfanyl)furan-2-yl]-2,4,6,7,8,9-hexahydropyrazolo[3,4-b]-1,7-naphtyridin-5-one trifluoroacetic acid

Conditions	Yield
Stage #1: tert-butyl 3,5-dioxopiperidine- 1-carboxylate; 3-aminopyrazole; 5-((1H-benzo[d]imidazol-2-yl)thio)furan-2-carbaldehyde In ethanol for 0.5h; Reflux; Stage #2: trifluoroacetic acid In dichloromethane at 20℃; for 1h;

tert-butyl 3,5-dioxopiperidine- 1-carboxylate (396731-40-1) + 3-aminopyrazole (1820-80-0) + 2-Fluorobenzaldehyde (446-52-6) + trifluoroacetic acid (76-05-1) → 4-(2-fluorophenyl)-2,4,6,7,8,9-hexahydropyrazolo[3,4-b]-1,7-naphtyridin-5-one trifluoroacetic acid

Conditions	Yield
Stage #1: tert-butyl 3,5-dioxopiperidine- 1-carboxylate; 3-aminopyrazole; 2-Fluorobenzaldehyde In ethanol for 0.5h; Reflux; Stage #2: trifluoroacetic acid In dichloromethane at 20℃; for 1h;

tert-butyl 3,5-dioxopiperidine- 1-carboxylate (396731-40-1) + 3-aminopyrazole (1820-80-0) + trifluoroacetic acid (76-05-1) + 3-(3,5-dichloro-phenoxy)-benzaldehyde → 4-[3-(3,5-dichlorophenoxy)phenyl]-2,4,6,7,8,9-hexahydropyrazolo[3,4-b]-1,7-naphtyridin-5-one trifluoroacetic acid

Conditions	Yield
Stage #1: tert-butyl 3,5-dioxopiperidine- 1-carboxylate; 3-aminopyrazole; 3-(3,5-dichloro-phenoxy)-benzaldehyde In ethanol for 0.5h; Reflux; Stage #2: trifluoroacetic acid In dichloromethane at 20℃; for 1h;

tert-butyl 3,5-dioxopiperidine- 1-carboxylate (396731-40-1) + 3-aminopyrazole (1820-80-0) + 3-Phenoxybenzaldehyde (39515-51-0) + trifluoroacetic acid (76-05-1) → 4-(3-phenoxyphenyl)-2,4,6,7,8,9-hexahydropyrazolo[3,4-b]-1,7-naphtyridin-5-one trifluoroacetic acid

Conditions	Yield
Stage #1: tert-butyl 3,5-dioxopiperidine- 1-carboxylate; 3-aminopyrazole; 3-Phenoxybenzaldehyde In ethanol for 0.5h; Reflux; Stage #2: trifluoroacetic acid In dichloromethane at 20℃; for 1h;

tert-butyl 3,5-dioxopiperidine- 1-carboxylate (396731-40-1) + 3-aminopyrazole (1820-80-0) + 3-(4-methoxyphenoxy)benzaldehyde (62373-80-2) + trifluoroacetic acid (76-05-1) → 4-[3-(4-methoxyphenoxy)phenyl]-2,4,6,7,8,9-hexahydropyrazolo[3,4-b]-1,7-naphtyridin-5-one trifluoroacetic acid

Conditions	Yield
Stage #1: tert-butyl 3,5-dioxopiperidine- 1-carboxylate; 3-aminopyrazole; 3-(4-methoxyphenoxy)benzaldehyde In ethanol for 0.5h; Reflux; Stage #2: trifluoroacetic acid In dichloromethane at 20℃; for 1h;

tert-butyl 3,5-dioxopiperidine- 1-carboxylate (396731-40-1) + 3-aminopyrazole (1820-80-0) + trifluoroacetic acid (76-05-1) + 3-(3,4-dichlorophenoxy)benzaldehyde (79124-76-8) → 4-[3-(3,4-dichlorophenoxy)phenyl]-2,4,6,7,8,9-hexahydropyrazolo[3,4-b]-1,7-naphtyridin-5-one trifluoroacetic acid

Conditions	Yield
Stage #1: tert-butyl 3,5-dioxopiperidine- 1-carboxylate; 3-aminopyrazole; 3-(3,4-dichlorophenoxy)benzaldehyde In ethanol for 0.5h; Reflux; Stage #2: trifluoroacetic acid In dichloromethane at 20℃; for 1h;

tert-butyl 3,5-dioxopiperidine- 1-carboxylate (396731-40-1) + 3-amino-2-ethoxycarbonylpyrrole hydrochloride + 5-((1H-benzo[d]imidazol-2-yl)thio)furan-2-carbaldehyde (39689-08-2) → 9-[5-(1H-benzimidazol-2-ylsulfanyl)uran-2-yl]-8-oxo-4,5,6,7,8,9-hexahydro-2H-pyrrolo[3,4-b]-1,7-naphthyridine-3-carboxylic acid ethyl ester hydrochloride

Conditions	Yield
Multi-step reaction with 2 steps 1: N-ethyl-N,N-diisopropylamine / ethanol / 0.5 h / Reflux 2: hydrogenchloride / 1,4-dioxane / 4 h View Scheme

tert-butyl 3,5-dioxopiperidine- 1-carboxylate (396731-40-1) + 3-amino-2-ethoxycarbonylpyrrole hydrochloride + 5-((1H-benzo[d]imidazol-2-yl)thio)furan-2-carbaldehyde (39689-08-2) → C29H29N5O6S

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In ethanol for 0.5h; Reflux;

tert-butyl 3,5-dioxopiperidine- 1-carboxylate (396731-40-1) + 3-amino-2-ethoxycarbonylpyrrole (252932-48-2) + 5-((1H-benzo[d]imidazol-2-yl)thio)furan-2-carbaldehyde (39689-08-2) → O6-tert-butyl O3-ethyl 9-[5-(1H-benzimidazol-2-ylsulfanyl)-2-furyl]-8-oxo-4,5,7,9-tetrahydro-2H-pyrrolo[3,4-b]-1,7-naphthyridine-3,6-dicarboxylate

Conditions	Yield
In butan-1-ol for 2h; Reflux;	6.9 g

tert-butyl 3,5-dioxopiperidine- 1-carboxylate (396731-40-1) → tert-butyl 2-amino-7-oxo-6,7-dihydro-4H-thiazolo[4,5-c]pyridine-5-carboxylate (478624-69-0)

Conditions	Yield
Multi-step reaction with 2 steps 1: N-Bromosuccinimide; 1,1'-azobis(1-cyanocyclohexanenitrile) / dichloromethane / 2 h / 0 °C / Inert atmosphere 2: triethylamine / methanol / 5.5 h / 20 °C / Inert atmosphere View Scheme
Multi-step reaction with 2 steps 1.1: N-Bromosuccinimide; 1,1'-azobis(1-cyanocyclohexanenitrile) / dichloromethane / 2 h / 0 °C / Inert atmosphere 2.1: methanol / 0.5 h / 20 °C / Inert atmosphere 2.2: 5 h / Reflux View Scheme

tert-butyl 3,5-dioxopiperidine- 1-carboxylate (396731-40-1) → tert-butyl 2-chloro-7-oxo-4,6-dihydrothiazolo[4,5-c]pyridine-5-carboxylate

Conditions	Yield
Multi-step reaction with 3 steps 1.1: N-Bromosuccinimide; 1,1'-azobis(1-cyanocyclohexanenitrile) / dichloromethane / 2 h / 0 °C / Inert atmosphere 2.1: triethylamine / methanol / 5.5 h / 20 °C / Inert atmosphere 3.1: isopentyl nitrite / acetonitrile / 0.17 h / 20 °C / Inert atmosphere 3.2: 5 h / -20 - 20 °C / Inert atmosphere View Scheme
Multi-step reaction with 3 steps 1.1: N-Bromosuccinimide; 1,1'-azobis(1-cyanocyclohexanenitrile) / dichloromethane / 2 h / 0 °C / Inert atmosphere 2.1: methanol / 0.5 h / 20 °C / Inert atmosphere 2.2: 5 h / Reflux 3.1: isopentyl nitrite / acetonitrile / 0.17 h / -20 °C / Inert atmosphere 3.2: 5 h / -20 - 20 °C View Scheme

tert-butyl 3,5-dioxopiperidine- 1-carboxylate (396731-40-1) → tert-butyl 2-methoxy-7-oxo-6,7-dihydro-4H-thiazolo[4,5-c]pyridine-5-carboxylate

Conditions	Yield
Multi-step reaction with 4 steps 1.1: N-Bromosuccinimide; 1,1'-azobis(1-cyanocyclohexanenitrile) / dichloromethane / 2 h / 0 °C / Inert atmosphere 2.1: triethylamine / methanol / 5.5 h / 20 °C / Inert atmosphere 3.1: isopentyl nitrite / acetonitrile / 0.17 h / 20 °C / Inert atmosphere 3.2: 5 h / -20 - 20 °C / Inert atmosphere 4.1: methanol / -78 - 20 °C / Inert atmosphere View Scheme
Multi-step reaction with 4 steps 1.1: N-Bromosuccinimide; 1,1'-azobis(1-cyanocyclohexanenitrile) / dichloromethane / 2 h / 0 °C / Inert atmosphere 2.1: methanol / 0.5 h / 20 °C / Inert atmosphere 2.2: 5 h / Reflux 3.1: isopentyl nitrite / acetonitrile / 0.17 h / -20 °C / Inert atmosphere 3.2: 5 h / -20 - 20 °C 4.1: sodium methylate / methanol / 0.75 h / -78 - 20 °C / Inert atmosphere View Scheme

tert-butyl 3,5-dioxopiperidine- 1-carboxylate (396731-40-1) → tert-butyl 3-methyl-2,7-dioxo-2,3,6,7-tetrahydro-4H-thiazolo[4,5-c]pyridine-5-carboxylate

Conditions

Yield

Multi-step reaction with 5 steps 1.1: N-Bromosuccinimide; 1,1'-azobis(1-cyanocyclohexanenitrile) / dichloromethane / 2 h / 0 °C / Inert atmosphere 2.1: triethylamine / methanol / 5.5 h / 20 °C / Inert atmosphere 3.1: isopentyl nitrite / acetonitrile / 0.17 h / 20 °C / Inert atmosphere 3.2: 5 h / -20 - 20 °C / Inert atmosphere 4.1: methanol / -78 - 20 °C / Inert atmosphere 5.1: pyridine / 0.5 h / 90 °C / Microwave irradiation 5.2: 3 h / 0 - 20 °C View Scheme

tert-butyl 3,5-dioxopiperidine- 1-carboxylate (396731-40-1) → tert-butyl 7-hydroxy-3-methyl-2-oxo-2,3,6,7-tetrahydro-4H-thiazolo[4,5-c]pyridine-5-carboxylate

Conditions

Yield

Multi-step reaction with 6 steps 1.1: N-Bromosuccinimide; 1,1'-azobis(1-cyanocyclohexanenitrile) / dichloromethane / 2 h / 0 °C / Inert atmosphere 2.1: triethylamine / methanol / 5.5 h / 20 °C / Inert atmosphere 3.1: isopentyl nitrite / acetonitrile / 0.17 h / 20 °C / Inert atmosphere 3.2: 5 h / -20 - 20 °C / Inert atmosphere 4.1: methanol / -78 - 20 °C / Inert atmosphere 5.1: pyridine / 0.5 h / 90 °C / Microwave irradiation 5.2: 3 h / 0 - 20 °C 6.1: sodium tetrahydroborate / methanol / 1 h / 0 °C / Inert atmosphere View Scheme

tert-butyl 3,5-dioxopiperidine- 1-carboxylate (396731-40-1) → tert-butyl 7-[allyloxy-(2-nitro-benzenesulfonyl)-amino]-3-methyl-2-oxo-2,3,6,7-tetrahydro-4H-thiazolo[4,5-c]pyridine-5-carboxylate

Conditions

Yield

Multi-step reaction with 7 steps 1.1: N-Bromosuccinimide; 1,1'-azobis(1-cyanocyclohexanenitrile) / dichloromethane / 2 h / 0 °C / Inert atmosphere 2.1: triethylamine / methanol / 5.5 h / 20 °C / Inert atmosphere 3.1: isopentyl nitrite / acetonitrile / 0.17 h / 20 °C / Inert atmosphere 3.2: 5 h / -20 - 20 °C / Inert atmosphere 4.1: methanol / -78 - 20 °C / Inert atmosphere 5.1: pyridine / 0.5 h / 90 °C / Microwave irradiation 5.2: 3 h / 0 - 20 °C 6.1: sodium tetrahydroborate / methanol / 1 h / 0 °C / Inert atmosphere 7.1: triphenylphosphine; di-tert-butyl-diazodicarboxylate / toluene / 4 h / 20 °C / Inert atmosphere View Scheme

Upstream product

• 873190-14-8 ethyl 2-(tert-butoxycarbonyl(2-oxopropyl)amino)acetate 

Downstream Products

• 478624-69-0 tert-butyl 2-amino-7-oxo-6,7-dihydro-4H-thiazolo[4,5-c]pyridine-5-carboxylate 

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