Studies On Synthesis Of DL-Isoserine And Preparation Of D-Cysteine Hydrochloride

DL-Isoserine and D-cysteine are two important pharmaceutical intermediates, which have been widely applied in medicine, food and other fields. In this paper, synthesis of DL-Isoserine as well as the production of D-cysteine hydrochloride was studied.A new synthesis method of DL-isoserine is designed and studied. The DL-isoserine was produced by ammonolysis of α-bromo-β-hydroxy propionic acid which was obtained by electrophilic addition of NBS to acrylic acid. The conditions of preparation for DL-isoserine were optimized, including temperature, ratio of raw material, reaction time and other factors. Total yield of DL-isoserine base on acrylic is 68.0%. And the preparation of DL-isoserine from reaction of tert-butyl hypochlorite with acrylic acid and ammonolysis subsequently was optimized. Under optimum conditions, the overall yield of DL-isoserine was increased to 70.0% from 28.8%.D-Cysteine is prepared by the asymmetric transformation based on previous laboratory study. L-Cysteine hydrochloride was neutralized with alkali to produce L-cysteine which reacted with acetone and L-tartaric acid obtaining R-2,2-dimethyl-4-thiazolidinecarboxylic acid L-tartarate i.e. D-DMTL-TA. Hydrolysis and reaction with MCI of D-DMTL-TA produce D-Cysteine. The conditions of preparation for D-Cysteine were optimized and the technology was enlarged. The overall yield base on L-Cysteine hydrochloride was increased to 59.2% from 45.9% with optical purity of 100%. Pilot-scale batch experiments and trial production were carried out. Several pilot-scale batch experiments research shows that the repeatability, yield and optical purity are little variation compared with laboratory research.