1-benzyl-4-(4-chloro-phenyl)-2,5-dihydro-1H-pyrrole-3-carboxylic acid monohydrate → (3S,4S)-1-Benzyl-4-(4-chloro-phenyl)-pyrrolidine-3-carboxylic acid

Participants

Reaction Conditions

Reaction Steps

A 12-l stainless steel autoclave was charged on air with 1-benzyl-4-(4-chloro-phenyl)-2,5-dihydro-1H-pyrrole-3-carboxylic acid monohydrate (180.0 g, 0.54 mol), [Ru(OAc)2((R)-2-Furyl-MeOBIPHEP)] (413.2 mg, 0.54 mmol, S/C 1,000) and methanol (7.1 l). The asymmetric hydrogenation was run for 20 h at 30° C. under 40 bar of hydrogen (99.3% conversion). After the pressure was released, a sample of the white suspension was evaporated to dryness affording crude (S,S)-Ia with 99.0% purity and >99.9% ee. The reaction suspension was concentrated to a volume of 1.8 l and stirred for 1 h at 0-5° C. After filtration, the filter cake was washed with cold methanol and dried on vacuum to yield 176.0 g (>99%) of (S,S)-Ia as a white solid with 99.0% purity and >99.9% ee.

Provenance & Evidence