1,2-Dichloroethane → (S)-3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)-phenyl)-2-(3-(methylsulfonamido)thiophene-2-carbonyloxy)ethyl)pyridine 1-oxide

Participants

Reaction Steps

A mixture of 3-(methylsulfonamido)thiophene-2-carboxylic acid (Int. 38) (110 mg, 0.497 mmol), (S)-3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)-phenyl)-2-hydroxyethyl)pyridine 1-oxide (209 mg, 0.497 mmol), EDC (286 mg, 1.491 mmol) and DMAP (30.4 mg, 0.249 mmol) in DCM (25 ml) was stirred at RT for 3 days. The mixture was diluted with DCM and washed with 1N HCl and aqueous NaHCO3; the organic layer was dried over Na2SO4, filtered and evaporated. The crude was purified by flash chromatography on silica gel cartridge (DCM/MeOH=99.5/0.5 to 99/1) affording (S)-3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)-phenyl)-2-(3-(methylsulfonamido)thiophene-2-carbonyloxy)ethyl)pyridine 1-oxide (Int. 39) (95 mg, 0.152 mmol, MS/ESI+623.05 [MH]+, [αD]=−28.6, c=0.3, DCM).

Provenance & Evidence