Thionyl Chloride → 2,5-Dichloro-4-[(4-chlorophenylsulfonyl)(2,6-difluorophenyl)methyl]pyridine

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Reaction Steps

The (2,5-dichloro-4-pyridyl)(2,6-difluorophenyl)methanol (744 mg, 2.57 mmol) obtained in Referential Example 53 was suspended in dichloromethane (6 ml), followed by the addition of thionyl chloride (0.5 ml) and dimethylformamide (one drop). The resulting mixture was stirred at room temperature for 5 hours. To the reaction mixture was added thionyl chloride (1.0 ml) further. The resulting mixture was stirred at room temperature for 24 hours. The reaction mixture was concentrated. The residue thus obtained was neutralized with a saturated solution of sodium bicarbonate and then, extracted with dichloromethane. The extract was washed with water and brine, dried over magnesium sulfate and concentrated. The residue thus obtained was dissolved in dimethylformamide (10 ml). After the addition of sodium 4-chlorobenzenesulfinate (613 mg, 3.08 mmol), the resulting mixture was heated at 50° C. for 5 hours and then, 80° C. for 3 hours. The reaction mixture was diluted with ethyl acetate. The diluted solution was washed with water and brine, dried over magnesium sulfate, and concentrated. The residue thus obtained was subjected to flash silica gel column chromatography. The fraction obtained from the hexane:ethyl acetate=4:1 eluate was concentrated. The resulting solid was recrystallized from diethyl ether-hexane to give the title compound (761 mg, 1.69 mmol, 66%) as a white solid.

Provenance & Evidence