反应详情

温度

80 °C

Combine Preparation 10 (trifluoro-methanesulfonic acid 3,5-dichloro-4-(1-cyclohexyl-2-oxo-pyrrolidin-3-ylmethyl)-phenyl ester) (250 mg, 0.53 mmol), 4-chlorocarbonylphenylboronic anhydride (263 mg, 0.53 mmol) and Pd(PPh3)4 (61 mg, 0.053 mmol) and purge with nitrogen. Add 2-(piperazin-1-yl)ethanol (0.32 mL, 2.6 mmol) followed quickly by dimethoxyethane (5 mL) and 2M sodium carbonate (1 mL) and heat to 80° C. for 1 hour. Cool to room temperature and pour into 1N sodium hydroxide. Extract with ethyl acetate and wash the organic layer twice with water, followed by brine. Dry over sodium sulfate and concentrate in vacuo. Purify on SCX column (load and wash with methanol, elute with 2M ammonia in methanol). Dissolve resultant oil in methylene chloride. Add 2M hydrochloric acid in ether (1 mL) and concentrate under vacuum. Re-dissolve in small amount of methylene chloride and add dropwise to vigorously stirred ether. Filter precipitate and dry in vacuum oven to afford 231 mg (74%) of the title compound: MS (m/z): 558 (M+).

1. custompurge with nitrogen
2. temperatureCool to room temperature
3. extractionExtract with ethyl acetate
4. washwash the organic layer twice with water
5. dry with materialDry over sodium sulfate
6. concentrationconcentrate in vacuo
7. customPurify on SCX column (load and wash with methanol, elute with 2M ammonia in methanol)
8. dissolutionDissolve resultant oil in methylene chloride
9. additionAdd 2M hydrochloric acid in ether (1 mL)
10. concentrationconcentrate under vacuum
11. additionRe-dissolve in small amount of methylene chloride and add dropwise to vigorously stirred ether
12. filtrationFilter precipitate
13. customdry in vacuum oven