(r)-5-Biphenyl-4-ylmethyl-3-[1-diisopropylamino-meth-(e)-ylidene]-2-oxo-pyrrolidine-1-carboxylic acid tert-butyl ester → (3R,5S)-5-biphenyl-4-ylmethyl-3-methyl-2-oxo-pyrrolidine-1-carboxylic acid tert-butyl ester

HRID 588298Notes

Reaction equation

HRID 588298 reaction equation
[C:1]([O:5][C:6]([N:8]1[C@H:12]([CH2:13][C:14]2[CH:19]=[CH:18][C:17]([C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=3)=[CH:16][CH:15]=2)[CH2:11]/[C:10](=[CH:26]\N(C(C)C)C(C)C)/[C:9]1=[O:34])=[O:7])([CH3:4])([CH3:3])[CH3:2].[H][H]>[Pd].CC([O-])=O.CC([O-])=O.[Pb+2].C(OCC)(=O)C>[C:1]([O:5][C:6]([N:8]1[C@H:12]([CH2:13][C:14]2[CH:15]=[CH:16][C:17]([C:20]3[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=3)=[CH:18][CH:19]=2)[CH2:11][C@@H:10]([CH3:26])[C:9]1=[O:34])=[O:7])([CH3:4])([CH3:2])[CH3:3].[C:1]([O:5][C:6]([N:8]1[C@H:12]([CH2:13][C:14]2[CH:15]=[CH:16][C:17]([C:20]3[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=3)=[CH:18][CH:19]=2)[CH2:11][C@H:10]([CH3:26])[C:9]1=[O:34])=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

6

Reactant 2

HCID 58160400(r)-5-Biphenyl-4-ylmethyl-3-[1-diisopropylamino-meth-(e)-ylidene]-2-oxo-pyrrolidine-1-carboxylic acid tert-butyl esterHCID 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 2

HCID 131709914Lindlars catalystCatalystHCID 8857Ethyl AcetateSolvent

Procedure

1.3 g (R)-5-Biphenyl-4-ylmethyl-3-[1-dimethylaminometh-(E/Z)-ylidene]-2-oxo-pyrrolidine-1-carboxylic acid tert-butyl ester (7-a, R1=Boc, R6=Me, R7=Me) is added to ethyl acetate (40 ml) at ambient temperature. 0.3 g of Lindlar Catalyst (ex Aldrich) is added to the mixture. The mixture is then pressurised under a hydrogen atmosphere to 2 bar. The mixture is stirred at ambient temperature and 2 bar hydrogen pressure for 3 days. The mixture is then filtered to remove the catalyst and concentrated under reduced pressure. The residue is then purified by column chromatography (ethyl acetate/hexane, 70:30) to afford (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 99.2:0.8 (3-a, R1=Boc: 3-b, R1=Boc) as determined by hplc.

Workup

  1. filtrationThe mixture is then filtered
  2. customto remove the catalyst
  3. concentrationconcentrated under reduced pressure
  4. customThe residue is then purified by column chromatography (ethyl acetate/hexane, 70:30)

Sources & evidence

ORD record
ord-a81042d6ae0046fa9133a00c143ce6a5
Source dataset
uspto-grants-2016_01
Patent number
US09227934B2

Reaction notes

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