Yield:-

Reaction Conditions:

with hydroxylamine hydrochloride;sodium hydroxide in methanol;water; pH=11 at -20 - 55;Large scale;

Steps:

3 Preparation of crude cycloserine
11.6 parts of hydroxylamine hydrochloride and 27.4 parts of purified water was added to the glass-lined reactor, cooled to less than -10 deg.] C, was added dropwise 75.9 parts by mass fraction of 30% aqueous sodium hydroxide solution, after addition is complete, stirring for 25 ~ 35min, drops add mass fraction of 50% D- chloro-serine methyl ester hydrochloride was added dropwise during controlling the feed temperature is less than -20 deg.] C, after the addition was complete, the reaction at -20 ~ -15 0.8 ~ 1.2h, the reaction after completed, the temperature was raised to 20 ~ 30 , PH adjusted to 11 to 25 ~ 30 , the reaction 3.8 ~ 4.2h, the reaction in the process of maintaining the PH 11; raised to 50 ~ 55 , the reaction was kept 25 ~ 35min, cooling to 25 ~ 30 , adjusted PH = 11.5 ± 0.2, and concentrated under reduced pressure to below 60 condenser or a small amount of drip dropping droplets, cooled to room temperature, the reaction vessel was added 157 parts of dry methanol and stirred 25 ~ 35min , centrifuged and the cake was washed with anhydrous methanol was added, and the filtrate combined filtrate and washed by centrifugation after the reaction was poured into a tank, cooled to -5 ~ 0 , PH adjusted to 6.4 ± 0.2, 0.8 ~ 1.2h stirring crystallization , the mixing process to keep PH value is maintained at 6.4 ± 0.2, centrifugation, dry methanol soaking, washing the filter cake, the cake reserved, cold smoked and dried to give crude cycloserine.

References:

Anhui Yuekang Hyatt Pharmaceutical Co., Ltd;Zhou, Ruguo;Liu, Weitan;Gao, Jie CN105646385, 2016, A Location in patent:Paragraph 0042; 0043; 0044; 0045

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