Pregabalin → Pregabalin Impurity 25

HRID 1259442Notes

Reaction equation

HRID 1259442 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

5

Reactant 3

HCID 5486971Pregabalin2×HCID 6436900Ethyl 5-methylhex-2-enoateHCID 14463328Ethyl 5-methyl-3-(nitromethyl)hexanoate

Product 1

HCID 24938718Pregabalin Impurity 25

Reagents, catalysts & solvents 1

HCID 6375NitromethaneSolvent

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%.

Workup

  1. customIn Synthesis 1989, 953
  2. customa synthesis of rac

Sources & evidence

ORD record
ord-909f1483f5ff4107b88b28915ed07aa4
Source dataset
uspto-grants-2013_06
Patent number
US08466297B2

Reaction notes

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