76513-69-4

Basic information

• Product Name: 2-(Trimethylsilyl)ethoxymethyl chloride
• Synonyms: SEM-CHLORIDE;SEM-CI;SEM-CL;CHLOROMETHYL 2-TRIMETHYLSILYLETHYL ETHER;2-(TRIMETHYLSILYL)ETHOXYMETHYL CHLORIDE;2-(CHLOROMETHOXY)ETHYLTRIMETHYLSILANE;2-chloromethyl 2-(trimethylsilyl)ethyl ether;2-(Trimethylsilyl)ethoxymethyl chloride, technical grade
• CAS NO: 76513-69-4
• Molecular Formula: C₆H₁₅ClOSi
• Molecular Weight: 166.72
• EINECS: 278-483-4
• Product Categories: Aliphatics;Biochemistry;Protection & Derivatization Reagents (for Synthesis);Reagents for Oligosaccharide Synthesis;Si (Classes of Silicon Compounds);Si-(C)4 Compounds;Silicon Compounds (for Synthesis);Synthetic Organic Chemistry
• Mol File: 76513-69-4.mol
• Article Data: 7

Chemical Properties

• Boiling Point: 170-172 °C(lit.)
• Flash Point: 116 °F
• Appearance: Clear colorless/Liquid
• Density: 0.942 g/mL at 25 °C(lit.)
• Vapor Pressure: 1.12mmHg at 25°C
• Refractive Index: n20/D 1.435(lit.)
• Storage Temp.: −20°C
• Solubility: Sol most organic solvents (pentane, CH2Cl2, Et2O, THF, DMF, DMPU, HMPA)
• Water Solubility: decomposes
• Sensitive: Moisture Sensitive
• BRN: 3587289
• CAS DataBase Reference: 2-(Trimethylsilyl)ethoxymethyl chloride(CAS DataBase Reference)
• NIST Chemistry Reference: 2-(Trimethylsilyl)ethoxymethyl chloride(76513-69-4)
• EPA Substance Registry System: 2-(Trimethylsilyl)ethoxymethyl chloride(76513-69-4)

Safety Data

• Hazard Codes: C
• Statements: 10-34
• Safety Statements: 26-28-36/37/39-45-16
• RIDADR: UN 2920 8/PG 2
• WGK Germany: 3
• F: 8-10-21
• TSCA: No
• HazardClass: 3.2
• PackingGroup: III
• Hazardous Substances Data: 76513-69-4(Hazardous Substances Data)

Usage

Description

2-(Trimethylsilyl)ethoxymethyl chloride, also known as SEM-Cl, is a versatile reagent used for the preparation of protection groups for various functional groups in organic synthesis. It is a colorless to light yellow liquid with a density of 0.942 g/cm3 and a boiling point of 57-59 °C at 8 mmHg.

Uses

Used in Organic Synthesis:
2-(Trimethylsilyl)ethoxymethyl chloride is used as a protecting group for amines, alcohols, phenols, and carboxy groups in organic synthesis. It is particularly useful for protecting the nitrogen of amides and sulfonamides groups.
Used in the Preparation of Ethers:
2-(Trimethylsilyl)ethoxymethyl chloride is used as a reagent in the preparation of SEM-ethers, which are useful in various chemical reactions.
Used in the Synthesis of Laterifluorones:
2-(Trimethylsilyl)ethoxymethyl chloride serves as a phenol protecting group in the synthesis of laterifluorones, a class of natural products with potential biological activities.
Used in the Preparation of 1-(2-Trimethylsilanyl-ethoxymethyl)-1H-Imidazole:
2-(Trimethylsilyl)ethoxymethyl chloride reacts with 1H-imidazole to prepare 1-(2-trimethylsilanyl-ethoxymethyl)-1H-imidazole, which can be used in various chemical applications.
Used as an Electrophilic Formaldehyde Equivalent:
2-(Trimethylsilyl)ethoxymethyl chloride acts as an electrophilic formaldehyde equivalent in chemical reactions, allowing for the introduction of a formaldehyde group into a molecule.
Used as an Acyl Anion Equivalent:
2-(Trimethylsilyl)ethoxymethyl chloride can also function as an acyl anion equivalent, which is useful in various organic transformations.
Used in One-Carbon Homologations and Cyclizations:
2-(Trimethylsilyl)ethoxymethyl chloride is used as a reagent in one-carbon homologations and cyclizations, which are important reactions in organic chemistry for the formation of new carbon-carbon bonds and the synthesis of cyclic compounds.

Purification Methods

Dissolve SEMCl in pentane, dry it (MgSO4), evaporate and distil the residual oil in a vacuum. Stabilise it with 10ppm of diisopropylamine. Store it under N2 in a sealed container in a refrigerator. [Lipshutz & Pegram Tetrahedron Lett 21 3343 1980.]

InChI:InChI=1/C6H15ClOSi/c1-9(2,3)5-4-8-6-7/h4-6H2,1-3H3

Synthetic route

chloro-trimethyl-silane (75-77-4) + 1-bromo-2-(chloromethoxy)ethane (1462-35-7) → (2-trimethylethylsilylethoxy)methyl chloride (76513-69-4)

Conditions	Yield
Stage #1: 1-bromo-2-(chloromethoxy)ethane With magnesium for 4h; Reflux; Stage #2: chloro-trimethyl-silane at 20℃; Reagent/catalyst;	99%
Stage #1: 1-bromo-2-(chloromethoxy)ethane With n-butyllithium; methylmagnesium chloride In tetrahydrofuran; hexane at 20 - 30℃; for 0.333333h; Stage #2: chloro-trimethyl-silane In tetrahydrofuran; hexane at 20 - 30℃; for 0.333333h;	85.8%
Stage #1: 1-bromo-2-(chloromethoxy)ethane With n-butyllithium; butyl magnesium bromide In tetrahydrofuran; hexane at 15 - 30℃; for 0.333333h; Stage #2: chloro-trimethyl-silane In tetrahydrofuran; hexane at 30℃; for 0.333333h;	80.4%

formaldehyd (50-00-0) + 2-(Trimethylsilyl)ethanol (2916-68-9) → (2-trimethylethylsilylethoxy)methyl chloride (76513-69-4)

Conditions	Yield
With hydrogenchloride for 0.5h;	90%
With hydrogenchloride at 0℃;	87%
With hydrogenchloride for 0.433333h;	85%

1H-imidazole (288-32-4) + (2-trimethylethylsilylethoxy)methyl chloride (76513-69-4) → 1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazole (101226-33-9)

Conditions	Yield
Stage #1: 1H-imidazole With sodium hydride In tetrahydrofuran at 0 - 25℃; for 0.5h; Inert atmosphere; Stage #2: (2-trimethylethylsilylethoxy)methyl chloride In tetrahydrofuran at 0 - 25℃; for 14h; Inert atmosphere;	100%
Stage #1: 1H-imidazole With sodium hydride In tetrahydrofuran; mineral oil at 0 - 20℃; for 0.75h; Stage #2: (2-trimethylethylsilylethoxy)methyl chloride In tetrahydrofuran; mineral oil at 20℃;	93%
Stage #1: 1H-imidazole With potassium tert-butylate In dimethyl sulfoxide at 0℃; for 0.5h; Large scale; Stage #2: (2-trimethylethylsilylethoxy)methyl chloride In dimethyl sulfoxide at 0 - 15℃; for 16h; Large scale;	90%

1,5-anhydro-4,6-O-benzylidene-2-deoxy-D-ribo-hex-1-enopyranose (63598-38-9) + (2-trimethylethylsilylethoxy)methyl chloride (76513-69-4) → 1,5-anhydro-4,6-O-benzylidene-2-deoxy-3-O-<<2-(trimethylsilyl)ethoxy>methyl>-D-ribo-hex-1-enopyranose (76513-66-1)

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In dichloromethane	100%
With N-ethyl-N,N-diisopropylamine In dichloromethane for 5h; Ambient temperature;	100%

(2-trimethylethylsilylethoxy)methyl chloride (76513-69-4) + (1R,7aS)-tetrahydro-1-methyl-1-(hydroxymethyl)-1H,3H-pyrrolo<1,2-c>oxazol-3-one (123190-86-3) → (1R,7aS)-tetrahydro-1-methyl-1-<<2-(trimethylsilyl)ethoxy>methoxy>methyl-1H,3H-pyrrolo<1,2-c>oxazol-3-one (123190-87-4)

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In dichloromethane for 14h; Ambient temperature;	100%
With N-ethyl-N,N-diisopropylamine In dichloromethane at 23℃; Yield given;

(2-trimethylethylsilylethoxy)methyl chloride (76513-69-4) + N-(2-Allyl-phenyl)-4-hydroxy-butyramide (114877-74-6) → N-(2-Allyl-phenyl)-4-(2-trimethylsilanyl-ethoxymethoxy)-butyramide (114877-90-6)

Conditions	Yield
With 1H-imidazole In N,N-dimethyl-formamide	100%

(2-trimethylethylsilylethoxy)methyl chloride (76513-69-4) + methyl 3-bromo-5-chloro-2,4-dihydroxy-6-methylbenzoate (105427-88-1) → methyl 2,4-bis[2-(trimethylsilyl)ethoxymethoxy]-3-bromo-5-chloro-6-methylbenzoate (105427-90-5)

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In dichloromethane at 20℃;	100%
With N-ethyl-N,N-diisopropylamine In dichloromethane Yield given;

(2-trimethylethylsilylethoxy)methyl chloride (76513-69-4) + 7-(4-tert-Butyldimethylsiloxy-2-hydroxybutyl)-1,4-dioxa-8-thiaspiro<4.5>dec-6-ene (144617-49-2) → 7-<4-tert-Butyldimethylsilyloxy-2-(2-trimethylsilylethoxy)methoxybutyl>-1,4-dioxa-8-thiaspiro<4.5>dec-6-ene (144617-50-5)

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In dichloromethane for 14h; Ambient temperature;	100%

(2-trimethylethylsilylethoxy)methyl chloride (76513-69-4) + 14-acetylpodocarpa-8,11,13-trien-12-ol → 14-acetyl-12-<2'-(trimethylsilyl)ethoxymethoxy>podocarpa-8,11,13-triene (154843-48-8)

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In dichloromethane for 5h; Ambient temperature;	100%

(2-trimethylethylsilylethoxy)methyl chloride (76513-69-4) + ethyl (1R,2S,3R,4R)-2,3-dihydroxy-4-methoxy-5-methyl-2-(2-trimethylsilyl-3-furyl)cyclohex-5-ene-1-carboxylate (173396-52-6) → ethyl (1R,2S,3R,4R)-2-hydroxy-4-methoxy-5-methyl-3-(2-trimethylsilylethoxymethoxy)-2-(2-trimethylsilyl-3-furyl)cyclohex-5-ene-1-carboxylate (173289-89-9)

Conditions	Yield
With N-ethyl-N,N-diisopropylamine	100%
With N-ethyl-N,N-diisopropylamine In dichloromethane at 20℃; for 24h;	96%

(2-trimethylethylsilylethoxy)methyl chloride (76513-69-4) + (2S)-1-benzyloxy-2-butanol (117039-90-4) → [2-((S)-1-Benzyloxymethyl-propoxymethoxy)-ethyl]-trimethyl-silane (179944-03-7)

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In dichloromethane Ambient temperature;	100%

(2-trimethylethylsilylethoxy)methyl chloride (76513-69-4) + (2R,3S,4S,5R)-2,5-bis[N-(benzyloxycarbonyl)amino]-1,6-diphenyl-3,4-hexanediol (153223-10-0) → dibenzyl ((2R,3S,4S,5R)-1,6-diphenyl-3,4-bis((2-(trimethylsilyl)ethoxy)methoxy)hexane-2,5-diyl)dicarbamate (153181-18-1)

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide for 16h; Ambient temperature;	100%
With N-ethyl-N,N-diisopropylamine In dichloromethane at 0℃; Inert atmosphere; Reflux;	77%
With N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide for 18h; Ambient temperature;

4'-hydroxy-2'-methylacetophenone (6921-64-8) + (2-trimethylethylsilylethoxy)methyl chloride (76513-69-4) → 1-[4-Methyl-2-(2-trimethylsilanyl-ethoxymethoxy)-phenyl]-ethanone (180988-76-5)

Conditions	Yield
With sodium hydride In tetrahydrofuran at 0℃; for 1h;	100%

(2-trimethylethylsilylethoxy)methyl chloride (76513-69-4) + (4S)-4-((2R)-2-hydroxypent-4-enyl)-2,2-dimethyl-1,3-dioxolane (87318-96-5) → {2-[(R)-1-((S)-2,2-Dimethyl-[1,3]dioxolan-4-ylmethyl)-but-3-enyloxymethoxy]-ethyl}-trimethyl-silane (115843-76-0)

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In dichloromethane for 16h; Ambient temperature;	100%

(2-trimethylethylsilylethoxy)methyl chloride (76513-69-4) + (5Z,11E,13E)-(9S,10S)-1-(tert-Butyl-dimethyl-silanyloxy)-16-chloro-9-methoxy-15-(1-methoxy-1-methyl-ethoxy)-6,10,14-trimethyl-hexadeca-5,11,13-trien-4-ol (210774-79-1) → (3E,5E,11Z)-(7S,8S)-16-(tert-Butyl-dimethyl-silanyloxy)-1-chloro-8-methoxy-2-(1-methoxy-1-methyl-ethoxy)-3,7,11-trimethyl-13-(2-trimethylsilanyl-ethoxymethoxy)-hexadeca-3,5,11-triene (210774-80-4)

Conditions	Yield
With tetra-(n-butyl)ammonium iodide; diisopropylamine In dichloromethane for 2h; Heating;	100%

(2-trimethylethylsilylethoxy)methyl chloride (76513-69-4) + methyl 6-hydroxynaphthalene-2-carboxylate (17295-11-3) → 6-(2-trimethylsilanyl-ethoxymethoxy)-naphthalene-2-carboxylic acid methyl ester

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In dichloromethane at 0 - 20℃; for 6h;	100%

(2-trimethylethylsilylethoxy)methyl chloride (76513-69-4) + methyl 7-hydroxy-2-naphthalenecarboxylate (95901-05-6) → methyl 7-(2-trimethylsilyl-ethoxymethoxy)-naphthalene-2-carboxylate (188861-94-1)

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In dichloromethane at 0 - 20℃; for 6h;	100%

(2-trimethylethylsilylethoxy)methyl chloride (76513-69-4) + (2R,3S,4S,5R)-6-Benzyloxy-4,5-bis-(tert-butyl-dimethyl-silanyloxy)-2-methyl-1-phenylsulfanyl-hexan-3-ol (236427-73-9) → C38H68O5SSi3 (236427-74-0)

Conditions	Yield
With tetra-(n-butyl)ammonium iodide; N-ethyl-N,N-diisopropylamine In 1,2-dichloro-ethane for 6h; Heating;	100%

(2-trimethylethylsilylethoxy)methyl chloride (76513-69-4) + (2R,5S,8R,3E,6E)-8-tert-butyldimethylsilyloxy-2-chloroacetoxy-5-hydroxytrideca-4,6-dienyl 2,2-dimethylpropanoate (286930-16-3) → (2R,5S,8R,3E,6E)-8-tert-butyldimethylsilyloxy-2-chloroacetoxy-5-(2-trimethylsilyl)ethoxytrideca-4,6-dienyl 2,2-dimethylpropanoate (286930-17-4)

Conditions	Yield
With tetra-(n-butyl)ammonium iodide; N-ethyl-N,N-diisopropylamine In dichloromethane Substitution;	100%
With tetra-(n-butyl)ammonium iodide; N-ethyl-N,N-diisopropylamine In dichloromethane at 0 - 20℃;	100%

2-hydroxybromobenzene (95-56-7) + (2-trimethylethylsilylethoxy)methyl chloride (76513-69-4) → (2-((2-bromophenoxy)methoxy)ethyl)trimethylsilane

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In dichloromethane at 0℃; for 2h;	100%
With N,N-diethyl-N-isopropylamine In dichloromethane at 0 - 20℃;	95%
With aluminum oxide; potassium fluoride In 1,2-dimethoxyethane at 25℃;	92%

(2-trimethylethylsilylethoxy)methyl chloride (76513-69-4) + methyl (3S)-4-(4,4'-dimethoxytriphenyl)methoxy-3-hydroxybutanoate (332843-95-5) → methyl (3S)-4-(4,4'-dimethoxytriphenyl)methoxy-3-(2-trimethylsilylethoxy)methoxybutanoate (332843-96-6)

Conditions	Yield
With N-ethyl-N,N-diisopropylamine	100%
With N-ethyl-N,N-diisopropylamine In dichloromethane at 0 - 20℃; Inert atmosphere;	99%

(2-trimethylethylsilylethoxy)methyl chloride (76513-69-4) + N-benzyloxycarbonyl-C-(2H-tetrazol-5-yl)methylamine → N-benzyloxycarbonyl-C-[2-(trimethylsilylethoxy)methyl-2H-tetrazol-5-yl]methylamine

Conditions	Yield
Stage #1: N-benzyloxycarbonyl-C-(2H-tetrazol-5-yl)methylamine With caesium carbonate In methanol at 20℃; for 2h; deprotonation; Stage #2: (2-trimethylethylsilylethoxy)methyl chloride In N,N-dimethyl-formamide at 20℃; for 18h; Alkylation; Further stages.;	100%

(2-trimethylethylsilylethoxy)methyl chloride (76513-69-4) + (S)-2-((4R,5S)-4,8-Dimethyl-spiro[4.5]deca-1,7-dien-1-yl)-2-hydroxy-propionic acid (1R,2S,5R)-5-methyl-2-(1-methyl-1-phenyl-ethyl)-cyclohexyl ester (306292-47-7) → (S)-2-((4R,5S)-4,8-Dimethyl-spiro[4.5]deca-1,7-dien-1-yl)-2-(2-trimethylsilanyl-ethoxymethoxy)-propionic acid (1R,2S,5R)-5-methyl-2-(1-methyl-1-phenyl-ethyl)-cyclohexyl ester (306292-53-5)

Conditions	Yield
With tetra-(n-butyl)ammonium iodide; N-ethyl-N,N-diisopropylamine In dichloromethane at 50℃; for 14h;	100%
With 1-amino-3-methylbutane; tetra-(n-butyl)ammonium iodide In dichloromethane at 50℃; for 14h;	100%

(2-trimethylethylsilylethoxy)methyl chloride (76513-69-4) + (5R,6R)-6-hydroxymethyl-5-[(1E)-3-[(4-methoxyphenyl)methoxy]-1-[[[tris-(1-methylethyl)silyl]oxy]methyl]-1-propenyl]-2-(2-nitrophenyl)-2-cyclohexen-1-one (482351-14-4) → (5R,6R)-5-[(1E)-3-[(4-methoxyphenyl)methoxy]-1-[[[tris-(1-methylethyl)silyl]oxy]methyl]-1-propenyl]-2-(2-nitrophenyl)-6-[[[2-(trimethylsilyl)ethoxy]methoxy]methyl]-2-cyclohexen-1-one (482351-22-4)

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In dichloromethane at 20℃; for 24h;	100%
With N-ethyl-N,N-diisopropylamine In dichloromethane at 20℃; for 24h;	100%

(2-trimethylethylsilylethoxy)methyl chloride (76513-69-4) + 1,1,1,3,3,3-hexafluoro-2-(1,3-thiazol-2-yl)propan-2-ol (362718-79-4) → 2-{1-trifluoromethyl-1-[(2-trimethylsilylethoxy)methoxy]-2,2,2-trifluoroethyl}thiazole (362718-80-7)

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In dichloromethane at 20℃; for 48h;	100%

(2-trimethylethylsilylethoxy)methyl chloride (76513-69-4) + (3aR,5aR,6S,9S,9aR,9bR)-9-(tert-butyldimethylsiloxy)-3,3a,4,5a,6,7,8,9,9a,9b-decahydro-6-hydroxy-9b-[3-(methoxymethoxy)propyl]-2,3,3,5a-tetramethyl-5H-benz[e]inden-5-one (607406-42-8) → (3aR,5aR,6S,9S,9aR,9bR)-9-(tert-butyldimethylsiloxy)-3,3a,4,5a,6,7,8,9,9a,9b-decahydro-9b-[3-(methoxymethoxy)propyl]-2,3,3,5a-tetramethyl-6-[[2-(trimethylsilyl)ethoxy]methoxy]-5H-benz[e]inden-5-one (607406-43-9)

Conditions	Yield
With N-ethyl-N,N-diisopropylamine; tetra-(n-butyl)ammonium iodide In dichloromethane at 20℃;	100%

N-(2-iodo-4-methoxyphenyl)-1-{tert-butyloxycarbonyl}pyrrolidine-3-carboxamide (862885-09-4) + (2-trimethylethylsilylethoxy)methyl chloride (76513-69-4) → N-(2-(trimethylsilyl)ethoxymethyl)-N-[2-iodo-4-methoxyphenyl]-1-{tert-butyloxycarbonyl}pyrrolidine-3-carboxamide (862885-17-4)

Conditions	Yield
With sodium hydride In tetrahydrofuran at 20℃; for 3h;	100%

7-Azaindole (271-63-6) + (2-trimethylethylsilylethoxy)methyl chloride (76513-69-4) → 1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrrolo[2,3-b]pyridine (879132-46-4)

Conditions	Yield
Stage #1: 7-Azaindole With sodium hydride In N,N-dimethyl-formamide; mineral oil at 0℃; for 1.25h; Stage #2: (2-trimethylethylsilylethoxy)methyl chloride In N,N-dimethyl-formamide; mineral oil for 1.25h;	100%
Stage #1: 7-Azaindole With sodium hydride In N,N-dimethyl-formamide; mineral oil at 0℃; for 1.25h; Stage #2: (2-trimethylethylsilylethoxy)methyl chloride In N,N-dimethyl-formamide; mineral oil for 1.25h;	100%
Stage #1: 7-Azaindole With sodium hydride In N,N-dimethyl-formamide; mineral oil at 0℃; for 1h; Stage #2: (2-trimethylethylsilylethoxy)methyl chloride In N,N-dimethyl-formamide; mineral oil for 1h;	100%

(2S,4S)-2-(4-chlorobenzyloxymethyl)-4-(1-chloroisoquinoline-5-sulfonylamino)-pyrrolidine-1-carboxylic acid tert-butyl ester (874447-84-4) + (2-trimethylethylsilylethoxy)methyl chloride (76513-69-4) → (2S,4S)-2-(4-chlorobenzyloxymethyl)-4-[(1-chloroisoquinoline-5-sulfonyl)-(2-trimethylsilylethoxymethyl)amino]-pyrrolidine-1-carboxylic acid tert-butyl ester (874447-86-6)

Conditions	Yield
With sodium hydride In tetrahydrofuran at 0℃; for 1.5h;	100%

2-bromophenylethyl alcohol (1074-16-4) + (2-trimethylethylsilylethoxy)methyl chloride (76513-69-4) → {2-[2-(2-bromo-phenyl)-ethoxymethoxy]-ethyl}-trimethyl-silane (900812-81-9)

Conditions	Yield
With N-ethyl-N,N-diisopropylamine	100%

8-bromo-6-methoxy-4-oxo-1,4-dihydroquinoline-2-carboxylic acid methyl ester (442549-50-0) + (2-trimethylethylsilylethoxy)methyl chloride (76513-69-4) → 8-bromo-6-methoxy-4-(2-trimethylsilanyl-ethoxymethoxy)-quinoline-2-carboxylic acid methyl ester (442549-51-1)

Conditions	Yield
With sodium hydride In 1-methyl-pyrrolidin-2-one at 20℃; for 2.5h;	100%
In 1-methyl-pyrrolidin-2-one
In 1-methyl-pyrrolidin-2-one
In 1-methyl-pyrrolidin-2-one

ethyl 1H-imidazole-2-carboxylate (33543-78-1) + (2-trimethylethylsilylethoxy)methyl chloride (76513-69-4) → ethyl 1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazole-2-carboxylate (329984-05-6)

Conditions	Yield
With sodium hydride In N,N-dimethyl-formamide at 0 - 25℃; for 12h; Concentration; Reagent/catalyst; Solvent; Temperature; Inert atmosphere;	100%
Stage #1: ethyl 1H-imidazole-2-carboxylate With sodium hydride In tetrahydrofuran; mineral oil at 0℃; for 0.333333h; Inert atmosphere; Stage #2: (2-trimethylethylsilylethoxy)methyl chloride In tetrahydrofuran; mineral oil at 0 - 20℃; for 2.5h; Inert atmosphere;	95%
With potassium carbonate In acetone at 0 - 20℃; for 16h;	85%

Upstream product

• 50-00-0 formaldehyd 
• 2916-68-9 2-(Trimethylsilyl)ethanol 
• 75-77-4 chloro-trimethyl-silane 
• 1462-35-7 1-bromo-2-(chloromethoxy)ethane 

Downstream Products

• 139975-85-2 3-<<2-(trimethylsilyl)ethoxy>methyl>-2-phenylimidazole 
• 107913-74-6 2,4-bis<<2-(trimethylsilyl)ethoxy>methoxy>acetophenone 
• 91817-39-9 [2-(3-Methoxy-5-pentyl-phenoxymethoxy)-ethyl]-trimethyl-silane 
• 135360-11-1 4-Methyl-benzoic acid 2-trimethylsilanyl-ethoxymethyl ester 
• 110466-10-9 3-hydroxy-4-(2-trimethylsilylethoxymethoxy)benzaldehyde 
• 123674-70-4 2,6-Dimethyl-6-(2-trimethylsilanyl-ethoxymethyl)-cyclohexa-2,4-dienone 
• 173381-13-0 (5S,6S)-1-bromo-5,6-bis(2'-trimethylsilylethoxymethoxy)cyclohexa-1,3-diene 
• 216314-79-3 4,5-diiodo-1-[(2-(trimethylsilyl)ethoxy)methyl]-1H-imidazole 
• 343304-85-8 4-[2-dimethoxymethyl-5-(4-fluoro-phenyl)-1H-imidazol-4-yl]-pyridine 
• 398142-83-1 3-methoxy-5-(2-trimethylsilanylethoxymethoxy)benzaldehyde 
• 192767-03-6 2-(4-bromophenyl)-2-[2-(trimethylsilyl)ethoxymethoxy]-1,1,1,3,3,3-hexafluoropropane 
• 264871-53-6 (2S,3S,6S,8aR)-6-Benzo[1,3]dioxol-5-yl-3-(tert-butyl-dimethyl-silanyloxymethyl)-8a-methyl-2-phenyl-6-[1-(2-trimethylsilanyl-ethoxymethoxy)-allyl]-hexahydro-oxazolo[3,2-a]pyridin-5-one 
• 274694-70-1 methyl (2S)-(-)-2-((p-toluenesulfonyl)-(2-trimethylsilyl-ethoxymethyl)-amino)-6-benzyloxy-hexanoate 
• 284469-96-1 N^α-Cbz-N^ε-formyl-N^ε-[[2-(trimethylsilyl)ethoxy]methoxy]-D-lysine methyl ester 

Relevant articles and documents

A simple synthetic method of SEM-CI, an important intermediate of anti-myelofibrosis ruxolitinib

The invention discloses a simple synthetic method of SEM-CI, an important intermediate of anti-myelofibrosis ruxolitinib. A chloromethylation intermediate is synthesized by taking 2-bromoethanol as amain raw material, petroleum ether as a solvent, polyformaldehyde and hydrogen chloride as chloromethylation reagents and concentrated sulfuric acid as a water absorbing agent; A complex of Grignard reagent and butyllithium is used as base extraction bromide and reacts with trimethylchlorosilane to synthesize the target product in two steps. The simple synthetic method of the invention has the advantages of easily available raw materials, low cost, simple and convenient operation, high yield, less ''three wastes '', reasonable process and stable quality.

A 2 - (tri-silyl) b oxygen methyl chloride synthesis method

The invention discloses a synthetic method of 2-(trimethylsilyl)-ethoxymethyl chloride. The reaction equation in the method is shown in the specification. According to the synthetic method of 2-(trimethylsilyl)-ethoxymethyl chloride disclosed by the invention, reactions are performed in normal pressure states and easy to control. Raw materials are products easily obtained massively in the market. The raw materials are low in cost and high in purity. Finally, reaction is performed in an alkaline condition, and the product is stable and long in retention time in the alkaline condition.

Synthesis of Orelline

Orelline (1), a metabolite of the toadstool Cortinarius Orellanus Fries with 2,2'-bipyridine structure, has been synthesized by the following method.The easily accessible 2-bromo-3-hydroxypyridine (3) was converted into the corresponding methyl (SEM) ether 4 and coupled with Zn and NiCl2/Ph3P to form the bipyridine derivative 5 in 79percent yield.Due to the chelating effect of the two SEM-ether groups in 5, it was possible to form selectively the dilithium compound 6 by an exchange reaction with BuLi at -50 deg C in Et2O.Reaction of 6 with electrophiles at -20 deg C afforded the 4- and 4,4'-substituted bipyridines 7-14 in excellent-to-reasonable yield.Oxidations of 6 with 2-(phenylsulfonyl)-3-phenyloxaziridin and with bis(trimethylsilyl)peroxide gave the 4,4'-diol 9 in 22 and 10percent yield, respectively.Methanolysis of 9 directly afforded crystalline 1 in high yield, with properties identical with those of natural orelline.Formylation of 6 with N-formylmorpholine gave 45percent of the dicarbaldehyde 13.Removal of the SEM groups in 13 by hydrolysis afforded the dihydroxydicarbaldehyde 15 that could be oxidized to 1 with alkaline H2O2.Attempts to oxidize 1 to orellanine (2) with 35percent H2O2 according to a known procedure were unsuccessful (cf.Exper.Part).Compound 7 with two Me3Si groups in 4,4'-position gave after methanolysis the fluorescence dye 16 with an appreciable Stokes shift in cyclohexane.