Sulfuric Acid → Methyl 3-(3,4-Difluorobenzylcarbamoyl)-6-isopropoxy-1-(pyridin-2-ylmethyl)-1H-indole-2-carboxylate

Participants

Reaction Steps

A solution of 3-(3,4-difluorobenzylcarbamoyl)-6-hydroxy-1-(pyridin-2-ylmethyl)-1H-indole-2-carboxylic acid (Compound 225, crude 6.5 g) and concentrated H2SO4 (0.1 ml, catalytic amount) in MeOH (100 ml) was heated to 90° C. for 16 h. The mixture was cooled and the suspension was filtered. The filtrate was concentrated, diluted with EtOAc, washed with H2O and brine, dried over Na2SO4, and concentrated in vacuo to give a pale brown solid as the crude product. General Procedure N. To a solution of the crude product in DMF (10 ml) was added 2-iodopropane (2.2 ml, 22 mmol) and K2CO3 (1.8 g, 13.2 mmol). The reaction was stirred at room temperature for 16 h and was diluted with EtOAc, washed with H2O and brine, dried over Na2SO4, and concentrated in vacuo. The residue was purified by chromatography on silica gel (0→100% EtOAc-hexanes) to yield the title compound as a white solid.

Provenance & Evidence