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

HRID 1799775Notes

Reaction equation

O.[CH2:2]([N:9]1[CH2:13][C:12]([C:14]2[CH:19]=[CH:18][C:17]([Cl:20])=[CH:16][CH:15]=2)=[C:11]([C:21]([OH:23])=[O:22])[CH2:10]1)[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.[H][H]>CO>[CH2:2]([N:9]1[CH2:13][C@H:12]([C:14]2[CH:15]=[CH:16][C:17]([Cl:20])=[CH:18][CH:19]=2)[C@H:11]([C:21]([OH:23])=[O:22])[CH2:10]1)[C:3]1[CH:4]=[CH:5][CH:6]=[CH:7][CH:8]=1

Participants

Conditions

Temperature: 2.5 °C

Procedure

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.

Workup

customa sample of the white suspension was evaporated to dryness
customaffording crude (S,S)-Ia with 99.0% purity and >99.9% ee
concentrationThe reaction suspension was concentrated to a volume of 1.8 l
filtrationAfter filtration
washthe filter cake was washed with cold methanol
customdried on vacuum
customto yield 176.0 g (>99%) of (S,S)-Ia as a white solid with 99.0% purity and >99.9% ee

Sources & evidence

ORD record: ord-cf77f3c284a245279311f08e1105da5e
Source dataset: uspto-grants-2013_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08344161B2

Reaction notes

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