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发明公开
CN105348172A (S)-1-(4-甲氧基-3-乙氧基)苯基-2-甲磺酰基乙胺的制备及阿普斯特的制备方法 有权 质押

(S)-1-(4-甲氧基-3-乙氧基)苯基-2-甲磺酰基乙胺的制备及阿普斯特的制备方法
摘要：
本发明涉及一种(S)-1-(4-甲氧基-3-乙氧基)苯基-2-甲磺酰基乙胺的制备及阿普斯特的制备方法。利用4-甲氧基-3-乙氧基溴苯经格氏反应制备4-甲氧基-3-乙氧基苯基溴化镁、与甲磺酰基乙腈加成、水解、还原得到(R,S)-1-(4-甲氧基-3-乙氧基)苯基-2-甲磺酰基乙胺(Ⅲ)，再经拆分、过滤得到(S)-1-(4-甲氧基-3-乙氧基)苯基-2-甲磺酰基乙胺N-乙酰基-L-亮氨酸盐(Ⅳ),经中和后得到(S)-1-(4-甲氧基-3-乙氧基)苯基-2-甲磺酰基乙胺(Ⅱ)；将化合物Ⅱ进行亚酰胺化制得阿普斯特(Ⅰ)。本发明拆分后的母液循环利用转化为化合物Ⅳ，减少废液排放，绿色环保，降低成本。
摘要（英）：

The invention relates to preparation of (S)-1-(4-methoxy-3-ethoxy)phenyl-2-methylsulfonyl ethylamine and a preparation method of apremilast. 4-methoxy-3-ethoxy phenylmagnesium bromide is prepared from 4-methoxy-3-ethoxy bromobenzene through Grignard reaction; 4-methoxy-3-ethoxy phenylmagnesium bromide is in addition reaction with methylsulfonyl acetonitrile, and then hydrolysis and reduction are carried out, so that (R,S)-1-(4-methoxy-3-ethoxy)phenyl-2-methylsulfonyl ethylamine (III) is obtained; separation and filtering are carried out, so that (S)-1-(4-methoxy-3-ethoxy)phenyl-2-methylsulfonyl ethylamine N-acetyl-L-leucine salt (IV) is obtained; through neutralization, (S)-1-(4-methoxy-3-ethoxy)phenyl-2-methylsulfonyl ethylamine (II) is obtained; the compound (II) is subjected to imidization, so that apremilast (1) is obtained. The mother liquor obtained after separation is recycled and converted into a compound IV, so that discharge of waste liquid is reduced, environment friendliness is realized and the cost is reduced.

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