Unlock instant, AI-driven research and patent intelligence for your innovation.

A kind of preparation method of 2-chloro-1,1,1-trimethoxyethane

A technology of trimethoxyethane and methyl chloroacetate, applied in the field of synthesis of organic pharmaceutical intermediates, can solve the problems of long reaction time, difficult operation, many steps and the like, and achieves the effects of good quality, low price and easy operation

Active Publication Date: 2017-07-11
XINXIANG KEXIN CHEM CO LTD
View PDF2 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0008] Although this process route has mild reaction conditions, the yield is low, there are many steps, the reaction time is long, and the reaction system needs to be anhydrous, which brings certain difficulties to the operation.

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • A kind of preparation method of 2-chloro-1,1,1-trimethoxyethane
  • A kind of preparation method of 2-chloro-1,1,1-trimethoxyethane

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0021] Add 250mL of methanol and 100g (0.92mol) of methyl chloroacetate into a 1L reaction flask, stir to dissolve, cool down to -10~0°C, then add 127g (1.20mol) of trimethyl orthoformate, continue stirring, and slowly drop Add 36.5 g of concentrated sulfuric acid with a mass concentration of 98%. After the addition is complete, the temperature is raised to 35-45° C. and reacted for 2 hours. Gas chromatography monitors that the raw material methyl chloroacetate does not remain, and the reaction is stopped.

[0022] Concentrate the reaction solution in the previous step under reduced pressure at 45~55°C, remove the solvent, cool to room temperature, add to 500mL potassium hydroxide aqueous solution (0.05M), extract with ethyl acetate (250mL×2), and combine ethyl acetate phase, washed with 300mL saturated brine, added 30g of anhydrous sodium sulfate to the ethyl acetate phase, stirred for 2 hours, filtered to remove anhydrous sodium sulfate, and the filtrate was concentrated unde...

Embodiment 2

[0024] Add 250mL of methanol and 100g (0.92mol) of methyl chloroacetate into a 1L reaction flask, stir to dissolve, cool down to -10~0°C, then add 147g (1.39mol) of trimethyl orthoformate, continue stirring, and slowly drop Add 36.5 g of concentrated sulfuric acid with a mass concentration of 98%. After the addition is complete, the temperature is raised to 35-45° C. and reacted for 1.5 hours. Gas chromatography monitors that the raw material methyl chloroacetate does not remain, and the reaction is stopped.

[0025] Concentrate the above reaction solution under reduced pressure at 45~55°C, remove the solvent, cool to room temperature, add to 500mL sodium hydroxide aqueous solution (0.05M), extract with ethyl acetate (250mL×2), and combine ethyl acetate phase, washed with 300mL saturated brine, added 30g of anhydrous sodium sulfate to the ethyl acetate phase, stirred for 2 hours, filtered to remove anhydrous sodium sulfate, and concentrated the filtrate under reduced pressure a...

Embodiment 3

[0027] Add 250mL of ethanol and 100g (0.92mol) of methyl chloroacetate into a 1L reaction bottle, stir to dissolve, cool down to -10~0°C, then add 127g (1.20mol) of trimethyl orthoformate, continue stirring, and slowly drop Add 36.5 g of concentrated sulfuric acid with a mass concentration of 98%. After the addition is complete, the temperature is raised to 35-45° C. and reacted for 2 hours. Gas chromatography monitors that the raw material methyl chloroacetate does not remain, and the reaction is stopped.

[0028] Concentrate the reaction solution in the previous step at 55~60°C under reduced pressure, remove the solvent, cool to room temperature, add to 500mL potassium hydroxide aqueous solution (0.05M), extract with ethyl acetate (250mL×2), and combine the ethyl acetate phase, washed with 300mL saturated brine, added 30g of anhydrous sodium sulfate to the ethyl acetate phase, stirred for 2 hours, filtered to remove anhydrous sodium sulfate, and concentrated the filtrate unde...

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

PUM

No PUM Login to View More

Abstract

The invention discloses a 2-chlorine-1,1,1- trimethoxyethane preparing method. The method is characterized by comprising the steps of 1, dissolving methyl chloroacetate in an organic solvent, lowering the temperature to -10-0 DEG C, and adding trimethyl orthoformate while stirring; 2, adding concentrated sulfuric acid solution with the mass concentration of 98% dropwise to the solution obtained from the step 1 at -10-0 DEG C; 3, heating the solution obtained from the step 2 to 30-80 DEG C for reaction for 1-3 h till reaction ends; 4, conducting vacuum concentration on the reaction liquid obtained in the step 3, adding the concentrated liquid to aqueous alkali, conducting extraction with ethyl acetate, washing the obtained ethyl acetate solution with saturated saline solution, conducting anhydrous sodium sulfate drying, and conducting vacuum concentration again to dry to obtain colorless oily liquid 2-chlorine-1,1,1- trimethoxyethane. According to the method, the reaction condition is mild, reaction time is short, production efficiency is high, cost is low, and the yield and purity of generated 2-chlorine-1,1,1- trimethoxyethane are quite high.

Description

technical field [0001] The invention belongs to the technical field of synthesis of organic drug intermediates, and in particular relates to a preparation method of 2-chloro-1,1,1-trimethoxyethane. Background technique [0002] 2-Chloro-1,1,1-trimethoxyethane is a lively intermediate in organic synthesis, which can be used as ketal or lactone to synthesize various heterocyclic structures such as thiazole and oxazoline. In US2003187274A1, 2-chloro-1,1,1-trimethoxyethane and semicarbazide hydrochloride synthesized 3-chloromethyl-1,2,4-triazolin-5-one, as a new synthetic stopper An important intermediate of the emetic aprepitant. Aprepitant is the world's first neurokinin-1 (NK-1) receptor blocker against the adverse reactions of chemotherapy, which is superior to currently marketed antiemetics. [0003] For the preparation of 2-chloro-1,1,1-trimethoxyethane, document EP1371624 reports that trimethyl orthoformate and chlorine are used in the presence of sodium methoxide to sy...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

Application Information

Patent Timeline
no application Login to View More
Patent Type & Authority Patents(China)
IPC IPC(8): C07C41/30C07C43/12
CPCC07C41/30C07C43/12
Inventor 邓杰张津枫栾振中
Owner XINXIANG KEXIN CHEM CO LTD