Tetrafluoroboric acid → 3,5-Dichloro-2-fluoroisonicotinonitrile

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Reaction Steps

Sodium nitrite (3.17 g, 46.0 mmol) was added in small portions to a suspension of crude 2-amino-3,5-dichloroisonicotinonitrile (4.32 g) in tetrafluoroboric acid (60 mL, 806 mmol) at −10° C. over 1 h. The resultant mixture was stirred at −10° C. for 1 h, carefully quenched with ice and solid Na2CO3 and extracted with ethyl acetate (3×150 mL). The combined organic layers were washed with brine (100 mL), dried (MgSO4), concentrated to ˜20 mL in volume, triturated with dichloromethane (30 mL) and filtered. The filtrate was concentrated and purified by silica gel chromatography, loading with dichloromethane-hexanes (1:1) and eluting with 5 to 30% ethyl acetate in hexanes, to give 3,5-dichloro-2-fluoroisonicotinonitrile (1.60 g, 36% yield for 2 steps). 1H NMR (400 MHz, CDCl3) δ ppm 8.29 (1H, s); LC retention time: 2.758 min (analytical HPLC Method A).

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