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4-[(R)-3-Cyano-3-(3,5-dichloro-phenyl)-4,4,4-trifluoro-butyryl]-2-methyl-benzoic acid tert-butyl ester → 4-[(R)-4-(3,5-dichloro-phenyl)-4-trifluoromethyl-4,5-dihydro-3H-pyrrol-2-yl]-2-methyl-benzoic acid tert-butyl ester

HRID 589633
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HRID 589633 반응식
[C:1]([O:5][C:6](=[O:32])[C:7]1[CH:12]=[CH:11][C:10]([C:13](=O)[CH2:14][C@:15]([C:28]#[N:29])([C:20]2[CH:25]=[C:24]([Cl:26])[CH:23]=[C:22]([Cl:27])[CH:21]=2)[C:16]([F:19])([F:18])[F:17])=[CH:9][C:8]=1[CH3:31])([CH3:4])([CH3:3])[CH3:2]>C(O)C.[Ni].O>[C:1]([O:5][C:6](=[O:32])[C:7]1[CH:12]=[CH:11][C:10]([C:13]2[CH2:14][C@:15]([C:20]3[CH:25]=[C:24]([Cl:26])[CH:23]=[C:22]([Cl:27])[CH:21]=3)([C:16]([F:19])([F:18])[F:17])[CH2:28][N:29]=2)=[CH:9][C:8]=1[CH3:31])([CH3:4])([CH3:3])[CH3:2]
참가 물질실험 절차후처리출처 및 근거반응 노트

참가 물질

5

반응물 1

HCID 547617414-[(R)-3-Cyano-3-(3,5-dichloro-phenyl)-4,4,4-trifluoro-butyryl]-2-methyl-benzoic acid tert-butyl ester

생성물 1

HCID 547617404-[(R)-4-(3,5-dichloro-phenyl)-4-trifluoromethyl-4,5-dihydro-3H-pyrrol-2-yl]-2-methyl-benzoic acid tert-butyl ester수율 94.7%

시약·촉매·용매 3

HCID 935Nickel촉매HCID 702Ethanol용매HCID 962
Water
용매

실험 절차

Alternatively, the title compound can be obtained by carrying out the following experiment: To a vigorously stirred solution of 4-[(R)-3-Cyano-3-(3,5-dichloro-phenyl)-4,4,4-trifluoro-butyryl]-2-methyl-benzoic acid tert-butyl ester (150 mg) in ethanol (9 mL) was added Raney Nickel (1.44 g, 50% suspension in water, previously washed with dry ethanol) and the reaction was stirred at room temperature under hydrogen (1 atm) for 2 hours then under arong overnight. Then the solution was filtered over celite, and the resulting filtrate was concentrated in vacuo to give the title compound (138 mg) as a pale yellow oil. The crude product was purified by flash chromatography (15% dichloromethane in ethyl acetate) to afford 4-[(R)-4-(3,5-dichloro-phenyl)-4-trifluoromethyl-4,5-dihydro-3H-pyrrol-2-yl]-2-methyl-benzoic acid tert-butyl ester as a pale yellow oil (0.070 g). Chiral HPLC analysis (Chiralpack IA, Heptane:2-propanol:diethylamine=90:10:0.1, 1 ml/min, retention time 5.93 minutes (major enantiomer), 8.57 minutes (minor enantiomer).

후처리

  1. washpreviously washed with dry ethanol) and the reaction
  2. waitunder arong overnight
  3. filtrationThen the solution was filtered over celite
  4. concentrationthe resulting filtrate was concentrated in vacuo

출처 및 근거

ORD 기록
ord-22833aa4d95e4923a2c6f97921e4a06a
출처 데이터셋
uspto-grants-2016_01
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US09233920B2

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