Methanesulfonyl chloride → 4-(Chloromethyl)-3,5-difluoropyridine

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Reaction Steps

Under argon, 5.0 g of (3,5-difluoropyridine-4-yl)methanol (Example 114A, 34.5 mmol, 1 equivalent) were initially charged in 100 ml of dichloromethane at −20° C., and 5.7 ml of diisopropylethylamine (34.5 mmol, 1 equivalent) and 2.95 ml of methanesulphonyl chloride (37.9 mmol, 1.1 equivalent) were added in succession. The mixture was warmed to RT and stirred at RT for 16 h and then at 40° C. for 3 h. The reaction solution was then concentrated, and twice 50 ml of toluene were added and the mixture was re-concentrated. This gave 13 g (230% of theory) as a crude product which were reacted further without purification.

Provenance & Evidence