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

HRID 1666951Notes

Reaction equation

HRID 1666951 reaction equation
[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

Participants

6

Reactant 3

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

Product 1

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

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 15413tert-Butyl methyl etherSolvent

Procedure

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.

Workup

  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.

Sources & evidence

ORD record
ord-9f16f34957944c938df6553a8cb4d257
Source dataset
uspto-grants-2011_10
Patent number
US08044202B2

Reaction notes

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