1374416-96-2

Upstream product

• 1374416-95-1 (R)-benzyl 3-((R)-1-(((benzyloxy)carbonyl)(methyl)amino)-2-hydroxyethyl)pyrrolidine-1-carboxylate 
• 1374416-97-3 C₂₄H₃₀N₂O₇S 
• 10442-39-4 tetra-n-butylammonium cyanide 
• 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 
• 1374416-87-1 (S)-3-(methylamino)-3-((R)-pyrrolidin-3-yl)propanenitrile 

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.

N-methylative aziridine ring opening and the synthesis of (S)-3-methylamino-3-[(R)-pyrrolidin-3-yl]propanenitrile

The preparation of (S)-3-methylamino-3-[(R)-pyrrolidin-3-yl]propanenitrile (1), a key fragment of fluoroquinolone antibiotic PF-00951966 and others was achieved by N-methylative aziridine ring opening, addition of methyl group at the ring nitrogen, and ring-opening via a cyanide nucleophile in a single operation starting from bicyclic (R)-2-[(R)-pyrrolidine-3-yl]aziridine. The starting compound was elaborated from stereoselective conjugate addition of nitromethane to (R)-aziridine-2-yl acrylate followed by selective reduction without breaking the aziridine ring.