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

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Reaction Steps

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.

Provenance & Evidence