Stereoselective synthesis of (S)-3-(methylamino)-3-((R)-pyrrolidin-3-yl)propanenitrile.
J Org Chem
; 77(10): 4732-9, 2012 May 18.
Article
em En
| MEDLINE
| ID: mdl-22524537
ABSTRACT
(S)-3-(methylamino)-3-((R)-pyrrolidin-3-yl)propanenitrile (1) is a key intermediate in the preparation of PF-00951966, (1) a fluoroquinolone antibiotic for use against key pathogens causing community-acquired respiratory tract infections including multidrug resistant (MDR) organisms. The current work describes the development of a highly efficient and stereoselective synthesis of 1 in 10 steps with an overall yield of 24% from readily available benzyloxyacetyl chloride. Two key transformations in the synthetic sequence involve (a) catalytic asymmetric hydrogenation with chiral DM-SEGPHOS-Ru(II) complex to afford ß-hydroxy amide 11b in good yield (73%) and high stereoselectivity (de 98%, ee >99%) after recrystallization and (b) S(N)2 substitution reaction with methylamine to provide diamine 14 with inversion of configuration at the 1'-position in high yield (80%), after efficient purification using a simple acid/base extraction protocol.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Pirrolidinas
/
Fluoroquinolonas
/
Antibacterianos
/
Nitrilas
Idioma:
En
Ano de publicação:
2012
Tipo de documento:
Article