Dichloromethane → (4-Chloro-5-fluoro-3-methoxypyridin-2-yl)cyclopropylacetonitrile

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Reaction Steps

A solution of (4-tert-butoxy-5-fluoro-3-methoxypyridin-2-yl)cyclopropylacetonitrile (0.9 g, 3 mmol) [Example 8] and trifluoroacetic acid (2 mL) in dichloromethane was stirred at room temperature for 25 minutes. The solvent was removed in vacuo and the oily residue dissolved in 15 mL of dichloromethane and 2 mL of dimethylformamide. The resulting solution was cooled in an ice-bath and treated dropwise with phosphoryl chloride (2.4 mL). The solution was allowed to warm to ambient temperature and stirred overnight. The mixture was then poured onto ice and extracted with dichloromethane (2×20 mL). The combined extracts were washed with water, saturated sodium bicarbonate, water, dried over sodium sulfate, and concentrated in vacuo. The residue was purified by column chromatography, eluting with ethyl acetate/hexane (1:4) to provide the title compound (0.4 g, 60%). 1H NMR (400 MHz, CDCl3) δ 8.32 (s. 1H), 4.05 (s, 3H), 3.77 (d, 1H), 1.58-1.49 (m 1H), 0.80-0.71 (m, 1H), 0.68-0.55 (m, 2H), 0.52-0.43 (m, 1H). MSCI: m/z=241 (MH+).

Provenance & Evidence