An enantioselective synthesis of (S)-(+)-3-aminomethyl-5-methylhexanoic acid via asymmetric hydrogenation
An enantioselective synthesis of (S)-(+)-3-aminomethyl-5-methylhexanoic acid via asymmetric hydrogenation
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DOI：
10.1021/jo034397b
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发表时间：
2003-07-11
影响因子：
3.6
通讯作者：
Wade, RA
中科院分区：
文献类型：
--
作者：
Burk, MJ;de Koning, PD;Wade, RA
报道了（S）-（+）-3-氨甲基-5-甲基己酸（1，普瑞巴林）的一种对映选择性合成方法。关键步骤是用铑Me-DuPHOS催化剂对3-氰基-5-甲基己-3-烯酸盐2进行不对称氢化，以非常高的ee提供所需的（S）3-氰基-5-甲基己酸酯3。随后用多相镍催化剂对腈3进行氢化，以优异的总产率和纯度提供普瑞巴林1。
A concise enantioselective synthesis of (S)-(+)-3-aminomethyl-5-methylhexanoic acid (1, Pregabalin) has been developed. The key step is the asymmetric hydrogenation of a 3-cyano-5-methylhex-3-enoic acid salt 2 with a rhodium Me-DuPHOS catalyst, providing the desired (S)3-cyano-5-methylhexanoate 3 in very high ee. Subsequent hydrogenation of the nitrile 3 with a heterogeneous nickel catalyst provides Pregabalin 1 in excellent overall yield and purity.