p-Toluenesulfonic acid monohydrate → N-((2R)-2,3-Dihydroxypropoxy)-3,4-difluoro-2-((2-fluoro-4-iodophenyl)amino)benzamide

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Reaction Steps

N-((R)-2,2-Dimethyl-[1,3]dioxolan-4-ylmethoxy)-3,4-difluoro-2-(2-fluoro-4-iodo-phenylamino)-benzamide (0.210 g, 0.40 mmol) was suspended in 10:1 methanol/H2O and pTsOH.H2O (0.008 g, 0.04 mmol) was added. The mixture was stirred at ambient temperature for 18 hrs, during which all solids dissolved to give a colorless, clear solution. The solution was diluted with EtOAc. The organic solution was washed with sodium bicarbonate (2×), brine (1×) and dried over Na2SO4. After filtration, the filtrate was concentrated, and recrystallized from EtOAc and heptane. This solid was washed with heptane-CH2Cl2 (1:1 and dried in vacuo at 60 C to give N-((R)-2,3-Dihydroxy-propoxy)-3,4-difluoro-2-(2-fluoro-4-iodo-phenylamino)-benzamide as a white solid, (0.136 g, 70%). Product shrinks at 90.8 C, melts at 115–117° C. Analysis shows C, 40.92; H, 3.16; N, 5.41, F, 11.30; I, 23.92 (6.75% EtOAc, 0.96% heptane).

Provenance & Evidence