Isopropyl Acetate → (3R,5S)-5-biphenyl-4-ylmethyl-3-methyl-2-oxo-pyrrolidine-1-carboxylic acid tert-butyl ester

HRID 1477439Notes

Reaction equation

HRID 1477439 reaction equation
C(OC(C)C)(=O)C.[C:8]([O:12][C:13]([N:15]1[C@H:19]([CH2:20][C:21]2[CH:26]=[CH:25][C:24]([C:27]3[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=3)=[CH:23][CH:22]=2)[CH2:18][C:17](=[CH2:33])[C:16]1=[O:34])=[O:14])([CH3:11])([CH3:10])[CH3:9].[H][H]>[Rh]>[C:8]([O:12][C:13]([N:15]1[C@H:19]([CH2:20][C:21]2[CH:22]=[CH:23][C:24]([C:27]3[CH:28]=[CH:29][CH:30]=[CH:31][CH:32]=3)=[CH:25][CH:26]=2)[CH2:18][C@@H:17]([CH3:33])[C:16]1=[O:34])=[O:14])([CH3:11])([CH3:9])[CH3:10].[C:8]([O:12][C:13]([N:15]1[C@H:19]([CH2:20][C:21]2[CH:22]=[CH:23][C:24]([C:27]3[CH:28]=[CH:29][CH:30]=[CH:31][CH:32]=3)=[CH:25][CH:26]=2)[CH2:18][C@H:17]([CH3:33])[C:16]1=[O:34])=[O:14])([CH3:11])([CH3:9])[CH3:10]

Participants

6

Reactant 3

HCID 7915Isopropyl AcetateHCID 46193438(R)-5-Biphenyl-4-ylmethyl-3-methylene-2-oxo-pyrrolidine-1-carboxylic acid tert-butylesterHCID 178418361HCID 178418361, compound

Product 2

HCID 66739124(3R,5S)-5-biphenyl-4-ylmethyl-3-methyl-2-oxo-pyrrolidine-1-carboxylic acid tert-butyl esterHCID 66739152(3S,5S)-5-biphenyl-4-ylmethyl-3-methyl-2-oxo-pyrrolidine-1-carboxylic acid tert-butyl ester

Reagents, catalysts & solvents 1

HCID 23948RhodiumCatalyst

Procedure

Isopropyl acetate (1 ml) is added to a mixture of 100 mg (R)-5-biphenyl-4-ylmethyl-3-methylene-2-oxo-pyrrolidine-1-carboxylic acid tert-butyl ester (4-a, R1=Boc) and 10% rhodium on carbon (10 mg). Hydrogen gas (ambient pressure) is applied to the mixture. The mixture is stirred at ambient temperature and pressure for 50 h. The mixture is then filtered over Celites and washed with isopropyl acetate (2×0.5 ml). The mixture is then concentrated in vacuo to give (3R,5S)-5-biphenyl-4-ylmethyl-3-methyl-2-oxo-pyrrolidine-1-carboxylic acid tert-butyl ester (3-a, R1=Boc) and (3S,5S)-5-biphenyl-4-ylmethyl-3-methyl-2-oxo-pyrrolidine-1-carboxylic acid tert-butyl ester (3-b, R1=Boc). Diastereomer ratio 21:79 (3-a, R1=Boc: 3-b, R1=Boc) as determined by hplc. Spectroscopic data in described in WO/2008/083967, for example, Examples 14 and 18.

Workup

  1. filtrationThe mixture is then filtered over Celites
  2. washwashed with isopropyl acetate (2×0.5 ml)
  3. concentrationThe mixture is then concentrated in vacuo

Sources & evidence

ORD record
ord-1119bc54ac4f43cba7c417d23a700f10
Source dataset
uspto-grants-2016_08
Patent number
US09403766B2

Reaction notes

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