Water → 6-Chloro-1-(3,5-difluoro-benzyl)-1H-indole-3-carboxylic acid

HRID 1665807노트

반응식

HRID 1665807 반응식
[Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([C:20](=[O:25])C(F)(F)F)=[CH:7][N:8]2[CH2:11][C:12]2[CH:17]=[C:16]([F:18])[CH:15]=[C:14]([F:19])[CH:13]=2)=[CH:4][CH:3]=1.[H-].[Na+].[OH2:28]>CN(C=O)C.COC(C)(C)C>[Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([C:20]([OH:25])=[O:28])=[CH:7][N:8]2[CH2:11][C:12]2[CH:17]=[C:16]([F:18])[CH:15]=[C:14]([F:19])[CH:13]=2)=[CH:4][CH:3]=1

참가 물질

6

반응물 3

HCID 962WaterHCID 24758Sodium hydrideHCID 597568221-[6-Chloro-1-(3,5-difluoro-benzyl)-1H-indol-3-yl]-2,2,2-trifluoro-ethanone

생성물 1

HCID 597567046-Chloro-1-(3,5-difluoro-benzyl)-1H-indole-3-carboxylic acid수율 95.6%

시약·촉매·용매 2

HCID 6228Dimethylformamide용매HCID 15413tert-Butyl methyl ether용매

실험 절차

To a solution of 2.2 g (6.5 mmol) 1-[6-chloro-1-(3,5-difluoro-benzyl)-1H-indol-3-yl]-2,2,2-trifluoro-ethanone in 65 ml DMF were added 1.7 g (36 mmol) sodium hydride (50% in oil) at room temperature. After stirring for 5 min. 0.59 ml (33 mmol) water were added dropwise. Stirring was continued at room temperature for 45 min. The reaction mixture was diluted with 150 ml of tert-butyl methyl ether and extracted with two 150-ml portions of a 1 M aqueous solution of sodium hydroxide. The combined aqueous layers were acidified to pH 1 with concentrated hydrochloric acid solution and extracted with three 150-ml portions of ethyl acetate. The combined organic extracts were dried over sodium sulfate, filtered and concentrated in vacuo. The residue was dried in high vacuo at 80° C. to give 2.0 g (95%) of the crude title compound as a brown solid.

후처리

  1. stirringStirring
  2. waitwas continued at room temperature for 45 min
  3. extractionextracted with two 150-ml portions of a 1 M aqueous solution of sodium hydroxide
  4. extractionextracted with three 150-ml portions of ethyl acetate
  5. dry with materialThe combined organic extracts were dried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe residue was dried in high vacuo at 80° C.

출처 및 근거

ORD 기록
ord-b995525b19c849f98df5d7cf345a289a
출처 데이터셋
uspto-grants-2011_10
특허 번호
US08039624B2

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