N-(4-hydroxyphenyl)methanesulfonamide → (S)-3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-((4-(methylsulfonamido)-phenoxy)carbonyloxy)ethyl)pyridine 1-oxide

Participants

Reaction Steps

To a stirred solution of (S)-3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-((4-nitrophenoxy)carbonyloxy)ethyl)pyridine 1-oxide (prepared in an analogous manner to that described in Example 45, Step 4) (0.140 g, 0.239 mmol) in DCM (5 ml), a solution of N-(4-hydroxyphenyl)-methanesulfonamide (0.0672 g, 0.359 mmol) and DMAP (0.0438 g, 0.359 mmol) in DCM (5 ml) was added drop wise, and the reaction was stirred at RT for 3 hours. The solvent was evaporated and the resulting crude was purified by chromatography on silica gel column (DCM:MeOH=10:0.4). A second purification by crystallization from absolute ethanol was required to obtain (S)-3,5-dichloro-4-(2-(3-(cyclopropylmethoxy)-4-(difluoromethoxy)phenyl)-2-((4-(methylsulfonamido)-phenoxy)carbonyloxy)ethyl)pyridine 1-oxide as a brown solid (0.050 g, 0.079 mmol, 33% yield, MS/ESI+ 632.74 [MH]+, [αD]=−36.59, c=0.252, DCM).

Provenance & Evidence