(R)-3-氨基丁醇的合成工艺优化  

Optimized Synthetic Process of (R)-3-Aminobutanol

作　　者：陈港生 郭珩[2] 张福利[2] CHEN Gangsheng;GUO Heng;ZHANG Fuli(School of Chemistry and Chemical Engineering,Shanghai University of Engineering Science,Shanghai 201620;Shanghai Institute of Pharmaceutical Industry Co.,Ltd.,China State Institute of Pharmaceutical Industry,Shanghai 201203)

机构地区：[1]上海工程技术大学化学化工学院,上海201620 [2]中国医药工业研究总院,上海医药工业研究院有限公司,上海201203

出　　处：《中国医药工业杂志》2023年第12期1713-1717,共5页Chinese Journal of Pharmaceuticals

摘　　要：(R)-3-氨基丁醇[(R)-1]是合成多个药物的关键中间体,其合成工艺优化有重要意义。参照专利,以(R)-α-苯乙胺[(R)-3]为手性助剂,终产品为(S)-3-氨基丁醇。改用(S)-3,与4-羟基-2-丁酮(2)反应,在氢气、雷尼镍作用下制得(R)-3-[[(S)-1-苯乙基]氨基]-1-丁醇[(R)-5]与(S)-5,制备其盐酸盐,再用乙醇和乙酸乙酯(体积比3∶1)混合溶液重结晶,得到5盐酸盐,用氢氧化钠水溶液游离、乙酸异丙酯萃取得到5,经钯炭、甲酸铵脱除苄基得到1。优化后1的总收率为56.04%(以2计),化学纯度98.5%,ee值99%,适合工业化生产。(R)-3-aminobutanol[(R)-1]was a versatile intermediate of several drugs,and it was of great significance to optimize its synthetic process.According to a patent,the final product was(S)-3-aminobutanol instead of the required(R)-product if prepared with(R)-α-phenethylamine[(R)-3]as the chiral auxiliary agent.So,with(S)-3 as the chiral auxiliary agent,compound(R)-3-[[(S)-1-phenylethyl]amino]butan-1-ol[(R)-5]and(S)-5 were prepared by the reductive amination of 4-hydroxy-2-butanone(2),and then(R)-5 and(S)-5 were transformed into the corresponding hydrochlorides.After that,compounds 5 hydrochloride was isolated by recrystallization with a mixed solvent of ethanol and ethyl acetate(volume ratio=3∶1).After alkalization,compound 5 was underwnt the de-benzylation with palladium charcoal and ammonium formate to obtain compound 1 with a total yield of 56.04%(based on 2),a purity of 98.5%and ee of 99%.

关 键 词：药物中间体 (R)-3-氨基丁醇 (S)-α-苯乙胺 4-羟基-2-丁酮 

分 类 号：TQ460.6[化学工程—制药化工]