1374416-97-3

Upstream product

• 1374416-95-1 (R)-benzyl 3-((R)-1-(((benzyloxy)carbonyl)(methyl)amino)-2-hydroxyethyl)pyrrolidine-1-carboxylate 
• 124-63-0 methanesulfonyl chloride 
• 1374416-88-2 1-benzyl-3-(2-(benzyloxy)acetyl)pyrrolidin-2-one 
• 1374416-89-3 (S)-1-benzyl-3-((S)-2-(benzyloxy)-1-hydroxyethyl)pyrrolidin-2-one 
• 1374416-90-6 (S)-2-(benzyloxy)-1-((R)-1-benzylpyrrolidin-3-yl)ethanol 
• 1374416-91-7 (S)-2-(benzyloxy)-1-((R)-1-benzylpyrrolidin-3-yl)ethyl 4-nitrobenzenesulfonate 
• 1374416-92-8 (R)-2-(benzyloxy)-1-((R)-1-benzylpyrrolidin-3-yl)-N-methylethanamine 
• 501-53-1 benzyl chloroformate 

Downstream Products

• 1374416-96-2 (R)-benzyl 3-((S)-1-(((benzyloxy)carbonyl)(methyl)amino)-2-cyanoethyl)pyrrolidine-1-carboxylate 

Relevant academic research and scientific papers

Stereoselective synthesis of (S)-3-(methylamino)-3-((R)-pyrrolidin-3-yl) propanenitrile

(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 β-hydroxy amide 11b in good yield (73%) and high stereoselectivity (de 98%, ee >99%) after recrystallization and (b) S N2 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.