摘要
以L-苯丙氨酸(3)为原料,经Boc保护、酰氯化、取代、脱羧、氯代,"一锅"制得(S)-4-苯基-3-(叔丁氧羰基)氨基-1-氯-2-丁酮(6),优化条件下收率达70.4%。6经还原和环合得到(2R,3S)-4-苯基-1,2-环氧-3-叔丁氧羰基氨基丁烷(1)。对影响收率的碱的种类、反应温度、还原剂等因素进行了工艺优化,优化条件下收率85.7%,产品纯度99%。1及中间体的结构经^(1)H NMR、^(13)C NMR和ESI-MS确证。该工艺方法操作简单,原料价廉、收率高。
L-Phenyl-alamine was Boc-protected to afford N-Boc-L-phenyl-alamine after using an one-pot method including acylating chlorination,substitution,decarboxylation and chlorination.(S)-4-Phenyl-3-(N-Bocamino)-1-chloro-2-butanone 6 was obtained with a yield of 70.4%.Then (2R,3S)-4-phenyl-3-(N-Boc-amino)-1-oxirane-butane 1 was synthesized from compound ■ through reduction and cyclization with a yield of of 85.7%and a chromatographic purity of 99%.The affecting factors including the reaction temperature,the kinds of the base and the reductant were studied.The structures of the compound 1 and intermediates were characterized by1H NMR,13C NMR and ESI-MS.The preparation process was simple in operation,low in raw material cost,high yield.
作者
刘志
仲金璐
陈成
李响
程青芳
LIU Zhi;ZHONG Jin-lu;CHEN Cheng;LI Xiang;CHENG Qing-fang(Lianyungang Guike Pharmaceutical Co.,Ltd.,Lianyungang 222000,China;School of Pharmacy,Jiangsu Ocean University,Lianyungang 222005,China)
出处
《精细化工中间体》
CAS
2020年第6期45-48,60,共5页
Fine Chemical Intermediates
基金
连云港高新区科技计划项目(ZD201917)。
关键词
硫酸阿扎那韦
中间体
还原
环合
atazanavir sulfate
intermediate
reduction
cyclization
