Methylamine → 3-[(4-Chlorophenyl)sulfonyl]-3-(2,5-difluorophenyl)propyl N-Methylcarbamate

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Reaction Steps

The 3-[(4-chlorophenyl)sulfonyl]-3-(2,5-difluorophenyl)-1-propanol (200 mg, 0.576 mmol) obtained in Example 207 was dissolved in dichloromethane (4 ml), followed by the addition, of triethylamine (84.2 μl, 0.605 mmol) and 4-nitrophenyl chloroformate (122 mg, 0.605 mmol). The resulting mixture was stirred at room temperature for 15 hours. After addition of methylamine (a 2.00M tetrahydrofuran solution, 2.0 ml, 4.00 mmol), the mixture was stirred at room temperature for 24 hours. Methylamine (a 2.00M tetrahydrofuran solution, 3.0 ml, 4.00 mmol) was added and the mixture was stirred at room temperature for 5 hours. The reaction mixture was diluted with dichloromethane, washed successively with a saturated aqueous solution of sodium bicarbonate, water and brine, dried over magnesium sulfate and then, concentrated. The residue thus obtained was subjected to flash chromatography on a silica gel column, and the fraction obtained from the hexane:ethyl acetate=3:2 eluate was concentrated. The concentrate was purified further by high performance liquid chromatography (using a mixed solvent of water/acetonitrile/formic acid) to yield the title compound (62.1 mg, 0.154 mmol, 27%) as a colorless oil.

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