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Method for preparing chiral alpha-alkyl substituted glycine hydrochloride

A technology of glycine hydrochloride and hydrocarbyl substitution, applied in the field of synthesis of chiral amino acid hydrochloride, can solve the problems of high energy consumption, unsuitable for large-scale production and high requirements

Active Publication Date: 2014-06-25
LIAONING ASYMCHEM LAB CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

The resolution reagent used in this method can be recovered, and the process is simple, but the high temperature reaction has high requirements on equipment, high energy consumption, and the optical purity of the obtained product is unstable, and the yield is low, so it is not suitable for large-scale production

Method used

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  • Method for preparing chiral alpha-alkyl substituted glycine hydrochloride

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0034] A kind of preparation L-allylglycine hydrochloride The method is characterized in that the specific preparation steps are as follows:

[0035] (1) Condensation: Add 470kg (1g / 6mL) of toluene, 90kg (1.0eq) of (S)-camphor, and 116kg (1.5eq) of tert-butyl glycine as the main raw material into a 1000L reactor. After stirring, add 1.26 dropwise. kg boron trifluoride diethyl ether (0.015eq), after dripping, the temperature is raised to 90±5℃ to react; after the reaction is completed, the temperature is lowered, the system is washed with sodium bicarbonate solution to pH=7-8, and the organic phase is concentrated to obtain the product 141kg, yield 90.0%, gas chromatography purity (GC): 96.8%;

[0036] (2) Substitution: Add 400kg of tetrahydrofuran (1g / 10mL) and 26.6kg (1.4eq) of potassium tert-butoxide to a 1000L reactor, cool to -10±2℃, and add the main raw materials dropwise 45kg of tetrahydrofuran (1g / 2mL) solution 125kg, stir for 0.5 hour, add 28.7kg (1.4eq) of 3-bromopropene...

Embodiment 2

[0042] A kind of preparation D-ethyl glycine hydrochloride The method is characterized in that the specific preparation steps are as follows:

[0043] (1) Condensation: Add 66kg (1g / 1mL) of n-heptane, (S) 100kg (1.0eq) of camphor, and 86kg (1.0eq) of the main raw material tert-butyl glycine to a 500L reactor. After stirring, add dropwise 932g (0.01eq) of boron trifluoride ether, after dripping, raise the temperature to 80±2℃ for reaction; after the reaction is completed, the temperature is lowered, the system is washed with sodium bicarbonate solution to pH=7~8, and the organic phase is concentrated to obtain the product 155kg, yield 89.0%, gas chromatography purity (GC) 96.5%;

[0044] (2) Replacement: Add 103kg (1g / 6mL) of 2-methyltetrahydrofuran (1g / 6mL) and 7.2kg (1.0eq) of sodium tert-butoxide to a 500L reactor, cool to -20~10℃, and add the main raw materials dropwise. 20kg of 2-methyltetrahydrofuran (1g / 4mL) solution, 90kg, stir for 0.3 hours, add 8.2kg (1.0eq) of bromoetha...

Embodiment 3

[0050] A kind of preparation L-benzylglycine hydrochloride The method is characterized in that the specific preparation steps are as follows:

[0051] (1) Condensation: Add 870kg xylene (1g / 10mL), (S) camphor 100kg (1.0eq), and 155kg (1.8eq) of tert-butyl glycine as the main raw material into a 2000L reactor. After stirring, add three 1.86kg (0.02eq) of boron fluoride ether, after dripping, raise the temperature to 110±2℃ to react; after the reaction is completed, the temperature is lowered, the system is washed with sodium bicarbonate solution to pH=7~8, the organic phase is concentrated to obtain the product 160kg; yield 91.8%, gas chromatography purity (GC) 96.0%;

[0052] (2) Substitution: Add 266kg of methyl tert-butyl ether (1g / 12mL) and 28kg of potassium carbonate (1.8eq) to a 1000L reactor, cool to 10±2℃, and add the main raw materials dropwise 30kg of methyl tert-butyl ether (1g / 6mL) solution 164kg, stir for 1 hour, add 34.8kg of benzyl bromide (1.8eq) dropwise, drip at ...

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Abstract

The invention discloses a method for preparing chiral alpha-alkyl substituted glycine hydrochloride. The method comprises steps of: selecting commercialized or easily prepared tert-butyl glycinate as an initial raw material; inducing alpha position chiral alkyl substitution through a chiral adjuvant (S) camphor; carrying out chemical split to obtain alpha-alkyl substituted glycine ester; and finally hydrolyzing to obtain optically pure alpha-alkyl substituted glycine hydrochloride. R represents C1-C12 saturated or unsaturated alkyl, or C1-C12 saturated or unsaturated alkyl substituted phenyl. The method uses cheap and easily available raw materials, has high reaction yield, stable technical condition, simple operation and no pollution; the obtained product has an optical purity greater than 99%; therefore, the invention provides a new idea and method for large-scale production of amino acid with high chiral purity.

Description

(1) Technical field: [0001] The invention relates to a method for synthesizing chiral amino acid hydrochloride, in particular to a method for preparing chiral alpha-hydrocarbyl substituted glycine hydrochloride. (2) Background technology: [0002] Chiral amino acids are important intermediates for the synthesis of peptides and lactam antibiotics and other drugs. They are widely used in the fields of pharmaceutical synthesis, pesticide synthesis, food additives, new material synthesis, and the development of fine chemicals. However, most of the synthetic amino acids are racemates, and the two enantiomers of racemic amino acids often have significant differences in activity, metabolic processes, and toxicity, such as the infamous "thalar" in the mid-1950s ( Thalidomide (Thalidomide) is used as a sedative to eliminate early pregnancy reactions in pregnant women, but it was soon discovered that the babies born to pregnant women who took this drug were deformed. Studies have found tha...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07C227/34C07C227/18C07C229/30C07C229/08C07C229/36
Inventor 洪浩韦建陈元东
Owner LIAONING ASYMCHEM LAB CO LTD
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