Pyridine → 1-[6-Chloro-1-(3,5-difluoro-phenyl)-1H-indol-3-yl]-2,2,2-trifluoro-ethanone

HRID 898142Notes

Reaction equation

HRID 898142 reaction equation
[Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([C:11](=[O:16])[C:12]([F:15])([F:14])[F:13])=[CH:7][NH:8]2)=[CH:4][CH:3]=1.N1C=CC=CC=1.[F:23][C:24]1[CH:25]=[C:26](B(O)O)[CH:27]=[C:28]([F:30])[CH:29]=1>C(Cl)Cl.CC([O-])=O.CC([O-])=O.[Cu+2]>[Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([C:11](=[O:16])[C:12]([F:13])([F:14])[F:15])=[CH:7][N:8]2[C:26]2[CH:25]=[C:24]([F:23])[CH:29]=[C:28]([F:30])[CH:27]=2)=[CH:4][CH:3]=1

Participants

6

Reactant 3

HCID 1049PyridineHCID 2734338(3,5-Difluorophenyl)boronic acidHCID 224972521-(6-Chloro-3-indolyl)-2,2,2-trifluoroethanone

Product 1

HCID 866101631-[6-Chloro-1-(3,5-difluoro-phenyl)-1H-indol-3-yl]-2,2,2-trifluoro-ethanoneYield 71%

Reagents, catalysts & solvents 2

HCID 8895Cupric acetateCatalystHCID 6344DichloromethaneSolvent

Procedure

To a solution of 200 mg (0.807 mmol) 1-(6-chloro-1H-indol-3-yl)-2,2,2-trifluoro-ethanone (prepared from 6-chloro indole and trifluoroacetic anhydride, described in U.S. 2004067939 A1) in 8 ml CH2Cl2, 293 mg (1.615 mmol) Cu(OAc)2, 0.26 ml (3.23 mmol) pyridine and 383 mg (2.42 mmol) 3,5-difluorophenyl boronic acid were added. The reaction mixture was stirred at RT overnight, filtered on decalit, and concentrated under vacuo. Column chromatography over silica (hexane followed by 1:9 ethyl acetate hexane) provided 206 mg (71%) of 1-[6-chloro-1-(3,5-difluoro-phenyl)-1H-indol-3-yl]-2,2,2-trifluoro-ethanone as a light brown solid. This compound was put in suspension in 10 ml H2O and 1.2 g NaOH was added. The reaction mixture was stirred at 70° C. for 2 days, cooled down to RT, and acidified with aqueous HCl (1N) until ph=1. The product was extracted with CH2Cl2, and the organic phase dried over Na2SO4. Evaporation of the solvent under vacuo afforded 120 mg (70%) of 6-chloro-1-(3,5-difluoro-phenyl)-1H-indole-3-carboxylic acid as a white solid.

Workup

  1. filtrationfiltered on decalit
  2. concentrationconcentrated under vacuo

Sources & evidence

ORD record
ord-604f489da3f84c30ae07bf8463ec7e64
Source dataset
uspto-grants-2008_04
Patent number
US07351706B2

Reaction notes

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