反应详情

温度

0 °C

To a suspension of 6-cyano-2-(2-fluoro-4-trimethylsilanyl-phenylamino)-nicotinic acid methyl ester (13.1 g, 38.2 mmol) in methanol (285 mL) was added cobalt (II) chloride (18.2 g, 76.4 mmol). The reaction mixture was cooled to 0° C. and sodium borohydride (14.5 g, 382 mmol) was added in small portions over 20 minutes (CAUTION: EFFERVESCENCE). The reaction mixture was stirred at 0° C. for 1 hour. The reaction was quenched by the addition of concentrated hydrochloric acid (50 mL) and the mixture stirred at 0° C. for 10 minutes and at room temperature for 45 minutes. Diethylenetriamine (9 mL) was then added and the mixture stirred for a further 15 minutes. The reaction mixture was filtered to remove a white solid, which was washed with dichloromethane. The filtrate was concentrated in vacuo and the resultant residue was dissolved in ethyl acetate and washed with a saturated solution of sodium hydrogen carbonate, followed by water then brine. The organic phase was isolated, dried (Na2SO4), filtered and concentrated in vacuo to afford the title compound as a brown solid (13.2 g, 100%). LCMS (method B): RT=2.82 min, M+H+=348.

1. customThe reaction was quenched by the addition of concentrated hydrochloric acid (50 mL)
2. stirringthe mixture stirred at 0° C. for 10 minutes and at room temperature for 45 minutes
3. additionDiethylenetriamine (9 mL) was then added
4. stirringthe mixture stirred for a further 15 minutes
5. filtrationThe reaction mixture was filtered
6. customto remove a white solid, which
7. washwas washed with dichloromethane
8. concentrationThe filtrate was concentrated in vacuo
9. dissolutionthe resultant residue was dissolved in ethyl acetate
10. washwashed with a saturated solution of sodium hydrogen carbonate
11. customThe organic phase was isolated
12. dry with materialdried (Na2SO4)
13. filtrationfiltered
14. concentrationconcentrated in vacuo