Pregabalin → Pregabalin Impurity 25

Reaction equation

CC(C[C@H](CN)CC(O)=O)C.C(OC(=O)/C=C/CC(C)C)C.C([O:25][C:26](=[O:37])[CH2:27][CH:28]([CH2:33][N+:34]([O-:36])=[O:35])[CH2:29][CH:30]([CH3:32])[CH3:31])C>[N+](C)([O-])=O>[CH3:31][CH:30]([CH3:32])[CH2:29][C@H:28]([CH2:33][N+:34]([O-:36])=[O:35])[CH2:27][C:26]([OH:37])=[O:25]

Participants

Procedure

In Synthesis 1989, 953 a synthesis of rac.-Pregabalin, starting from (E)-5-methyl-hex-2-enoic acid ethyl ester, which was converted with nitromethane into 5-methyl-3-nitromethyl-hexanoic acid ethyl ester, has been reported. Subsequent catalytic hydrogenation followed by saponification leads to rac.-Pregabalin. Recently an enzymatic hydrolysis of this racemic nitro ester was carried out (Tetrahedron Asymmetry 2008, 19, 945). With enzyme Novozyme 435 enantiomerically enriched (S)-5-methyl-3-nitromethyl-hexanoic acid could be obtained in a good selectivity if the conversion was stopped at 30%.