Potassium Hydroxide → Pregabalin

HRID 1034568Notes

Reaction equation

HRID 1034568 reaction equation
C([O:3][C:4](=[O:15])[CH2:5][C@@H:6]([CH2:11][N+:12]([O-])=O)[CH2:7][CH:8]([CH3:10])[CH3:9])C.[OH-].[K+].[H][H]>O.[Ni]>[CH3:10][CH:8]([CH2:7][C@H:6]([CH2:11][NH2:12])[CH2:5][C:4]([OH:15])=[O:3])[CH3:9]

Participants

6

Reactant 3

HCID 14797Potassium HydroxideHCID 29984078(S)-5-methyl-3-nitromethyl-hexanoic acid ethyl esterHCID 178418361HCID 178418361, compound

Product 1

HCID 5486971PregabalinYield 80%

Reagents, catalysts & solvents 2

HCID 935NickelCatalystHCID 962WaterSolvent

Procedure

150 g of (S)-5-methyl-3-nitromethyl-hexanoic acid ethyl ester (VIII, R1=ethyl; assay: 97.2%) were suspended in 300 mL of H2O. KOH (90.1.g, assay 86.1%, 2.05 eq.) was added. The initially turbid reaction mixture became clear which indicated that the reaction was nearly completed. After complete conversion (as determined by HPLC) the reaction mixture was transferred to a hydrogenation reactor. 90.0 g of an aqueous slurry of Raney Nickel were added. At a hydrogen pressure of 12 bar and a temperature of 45° C. the mixture was stirred until complete conversion was detected by HPLC giving 88.0 g of pregabalin in an aqueous solution.

Workup

  1. customThe initially turbid reaction mixture
  2. customAfter complete conversion (as determined by HPLC) the reaction mixture was transferred to a hydrogenation reactor

Sources & evidence

ORD record
ord-ab1c7a7c0466476b95a5ae2f2d000067
Source dataset
uspto-grants-2013_10
Patent number
US08546112B2

Reaction notes

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