(R)-3-氨基丁醇的合成工艺优化
Optimized Synthetic Process of (R)-3-Aminobutanol
陈港生 1郭珩 2张福利2
作者信息
- 1. 上海工程技术大学化学化工学院,上海 201620;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
- 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
- 折叠
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.
Abstract
(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Key words
drug intermediate/(R)-3-aminobutanol/(S)-α-phenethylamine/4-hydroxy-2-butanone引用本文复制引用
出版年
2023
NETL
NSTL
万方数据