反应详情

温度

150 °C

2,6-dichloro-N-cyclohexylnicotinamide (Intermediate 1, 273 mg, 1 mmol) was stirred in 1,4-dioxane (4 ml). To this solution was added 4-fluorophenethyl alcohol (154 mg, 1.1 mmol) followed by bis-sodium hexamethyldisilylamide 1.0M in THF (1.1 ml, 1.1 mmol). The tube was sealed and subjected to microwave heating 150° C. (Biotage Initiator 300 W) for 2 hours. The solvent was evaporated and the residue was diluted with water (15 ml) and extracted with dichloromethane (2×20 ml). The combined extract was washed with brine (20 ml) dried over MgSO4, filtered and evaporated. The crude product was purified on SiO2 (40 g) eluting with ethyl acetate/isohexane 0-40% and gave 6-chloro-N-cyclohexyl-2-[2-(4-fluorophenyl)ethoxy]nicotinamide (153 mg, 40%) as a white solid

1. customThe tube was sealed
2. customThe solvent was evaporated
3. additionthe residue was diluted with water (15 ml)
4. extractionextracted with dichloromethane (2×20 ml)
5. extractionThe combined extract
6. washwas washed with brine (20 ml)
7. dry with materialdried over MgSO4
8. filtrationfiltered
9. customevaporated
10. customThe crude product was purified on SiO2 (40 g)
11. washeluting with ethyl acetate/isohexane 0-40%