反应详情

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+).

1. customThe solvent was removed in vacuo
2. dissolutionthe oily residue dissolved in 15 mL of dichloromethane
3. temperatureThe resulting solution was cooled in an ice-bath
4. additiontreated dropwise with phosphoryl chloride (2.4 mL)
5. additionThe mixture was then poured onto ice
6. extractionextracted with dichloromethane (2×20 mL)
7. washThe combined extracts were washed with water, saturated sodium bicarbonate, water
8. dry with materialdried over sodium sulfate
9. concentrationconcentrated in vacuo
10. customThe residue was purified by column chromatography
11. washeluting with ethyl acetate/hexane (1:4)