title: An enantioselective synthesis of (S)-(+)-3-aminomethyl-5-methylhexanoic acid via asymmetric hydrogenation.
abstract: 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.
authors.affiliation: Dowpharma, Chirotech Technology Limited, A Subsidiary of The Dow Chemical Company, Cambridge Science Park, Milton Road, Cambridge CB4 0WG, United Kingdom.
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Burk
authors.forename: Pieter D
authors.initials: PD
authors.lastname: De Koning
authors.forename: Todd M
authors.initials: TM
authors.lastname: Grote
authors.forename: Marvin S
authors.initials: MS
authors.lastname: Hoekstra
authors.forename: Garrett
authors.initials: G
authors.lastname: Hoge
authors.forename: Rex A
authors.initials: RA
authors.lastname: Jennings
authors.forename: William S
authors.initials: WS
authors.lastname: Kissel
authors.forename: Tung V
authors.initials: TV
authors.lastname: Le
authors.forename: Ian C
authors.initials: IC
authors.lastname: Lennon
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Mulhern
authors.forename: James A
authors.initials: JA
authors.lastname: Ramsden
authors.forename: Robert A
authors.initials: RA
authors.lastname: Wade
mesh_terms: D000927:Anticonvulsants / Q000138:chemical synthesis*; D001426:Bacterial Proteins; D006865:Hydrogenation; D000069583:Pregabalin; D013237:Stereoisomerism; D014157:Transcription Factors; D005680:gamma-Aminobutyric Acid / Q000031:analogs & derivatives* / Q000138:chemical synthesis*
chemical_list: D000927:Anticonvulsants; D001426:Bacterial Proteins; C442131:ScoC protein, Bacillus subtilis; D014157:Transcription Factors; D000069583:Pregabalin; D005680:gamma-Aminobutyric Acid