反应详情

Morpholine-4-carboxylic acid 1-[2-(4-fluorophenyl)acetyl]-pyrazolidin-4-yl ester, 41, (354 mg, 1.05 mmol) and 2-phenoxypyrimidine-4-carbonyl chloride, 18, (345 mg, 1.47 mmol) are dissolved in dichloromethane (2 mL). 1.0 N NaOH (3 mL) is added dropwise at room temperature while vigorously stirring. The reaction is allowed to proceed for 12 hours after which time additional acid chloride, 18, is added and stirring continued for 3 hours. Additional acid chloride, 18, (83 mg) is added and stirring continued for an additional 12 hours. After which time the reaction is diluted with dichloromethane (50 mL) and washed with water (50 mL). The combined organic layers are washed with NaHCO3 (sat.) (50 mL) and brine (50 mL), dried, filtered and concentrated to provide a brown oil. The crude material is purified over silica (100% ethyl acetate to 5% methyl alcohol/ethyl acetate) afford 348 mg (61% yield) of the desired product as a viscous oil.

1. stirringstirring
2. waitcontinued for 3 hours
3. stirringstirring
4. waitcontinued for an additional 12 hours
5. washwashed with water (50 mL)
6. washThe combined organic layers are washed with NaHCO3 (sat.) (50 mL) and brine (50 mL)
7. customdried
8. filtrationfiltered
9. concentrationconcentrated
10. customto provide a brown oil
11. customThe crude material is purified over silica (100% ethyl acetate to 5% methyl alcohol/ethyl acetate)