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

HRID 2198055ノート

反応式

HRID 2198055 の反応式
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

参加物

8

反応物 4

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

生成物 1

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

試薬・触媒・溶媒 3

HCID 167845palladium(II) acetate触媒HCID 962Water溶媒HCID 1140Toluene溶媒

実験手順

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.

後処理

  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)

出典と根拠

ORDレコード
ord-ace196af8f554a648528af1e8bc49f79
出典データセット
uspto-grants-2012_12
特許番号
US08338622B2

反応ノート

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