Cesium carbonate → (3S)-1-[4-chloro-2-(trifluoromethyl)phenyl]pyrrolidin-3-ol

HRID 2198055노트

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HRID 2198055 반응식
Br[C:2]1[CH:7]=[CH:6][C:5]([Cl:8])=[CH:4][C:3]=1[C:9]([F:12])([F:11])[F:10].[NH:13]1[CH2:17][CH2:16][C@H:15]([OH:18])[CH2:14]1.C1(P(C2C=CC=CC=2)C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(=O)([O-])[O-].[Cs+].[Cs+]>C1(C)C=CC=CC=1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.O>[Cl:8][C:5]1[CH:6]=[CH:7][C:2]([N:13]2[CH2:17][CH2:16][C@H:15]([OH:18])[CH2:14]2)=[C:3]([C:9]([F:12])([F:11])[F:10])[CH:4]=1

참가 물질

8

반응물 4

HCID 10796Cesium carbonateHCID 1361722-Bromo-5-chlorobenzotrifluorideHCID 634876Binap, (A+-)-HCID 2733874(3S)-pyrrolidin-3-ol

생성물 1

HCID 67022292(3S)-1-[4-chloro-2-(trifluoromethyl)phenyl]pyrrolidin-3-ol수율 81.3%

시약·촉매·용매 3

HCID 167845palladium(II) acetate촉매HCID 962Water용매HCID 1140Toluene용매

실험 절차

A solution of 1-bromo-4-chloro-2-(trifluoromethyl)benzene (15.0 g), (3S)-pyrrolidin-3-ol (5.0 g), palladium(II) acetate (561 mg), (±)-2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (3.11 g) and cesium carbonate (37.8 g) in toluene (280 ml) was stirred under an argon gas atmosphere at 100° C. for 18 hr. After cooling to room temperature, water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, and filtered. The filtrate was concentrated, and the residue was purified by silica gel column chromatography (hexane/ethyl acetate 95:5-80:20) to give the title compound (12.4 g, yield 81%) as a colorless oil.

후처리

  1. extractionthe mixture was extracted with ethyl acetate
  2. washThe organic layer was washed with saturated brine
  3. dry with materialdried over anhydrous magnesium sulfate
  4. filtrationfiltered
  5. concentrationThe filtrate was concentrated
  6. customthe residue was purified by silica gel column chromatography (hexane/ethyl acetate 95:5-80:20)

출처 및 근거

ORD 기록
ord-ace196af8f554a648528af1e8bc49f79
출처 데이터셋
uspto-grants-2012_12
특허 번호
US08338622B2

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