(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 588298노트

반응식

HRID 588298 반응식
[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]

참가 물질

6

반응물 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, 화합물

생성물 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

시약·촉매·용매 2

HCID 131709914Lindlars catalyst촉매HCID 8857Ethyl Acetate용매

실험 절차

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.

후처리

  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)

출처 및 근거

ORD 기록
ord-a81042d6ae0046fa9133a00c143ce6a5
출처 데이터셋
uspto-grants-2016_01
특허 번호
US09227934B2

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