反应详情

Dissolve 1037 mg (5.37 mmol) of (3R)-1-benzylpiperidin-3-ol [H. Tomori, Bull. Chem. Soc. Jpn. 69, 1, 207-216 (1996)] in 10 ml of THF and add 268 mg (6.71 mmol) of sodium hydride (60% in mineral oil). After 10 minutes, add a solution of 2000 mg (5.64 mmol) of 4-chloro-6-(2-fluorophenyl)-5-(4-methoxyphenyl)furo[2,3-d]pyrimidine in 10 ml of THF and 99 mg (0.27 mmol) of tetra-n-butylammonium iodide. Heat the reaction mixture under reflux for 16 hours. Then add 100 ml of water and 100 ml of ethyl acetate. Remove the organic phase and wash with 50 ml of 1N hydrochloric acid and 100 ml of satd. sodium chloride solution. Re-extract the aqueous phase with 50 ml of ethyl acetate, dry the combined organic extracts over sodium sulphate, filter and concentrate under reduced pressure. 2645 mg (89% of theory, 92% purity) of the desired product are obtained.

1. temperatureHeat the reaction mixture
2. temperatureunder reflux for 16 hours
3. customRemove the organic phase
4. washwash with 50 ml of 1N hydrochloric acid and 100 ml of satd
5. dry with materialRe-extract the aqueous phase with 50 ml of ethyl acetate, dry the combined organic extracts over sodium sulphate
6. filtrationfilter
7. concentrationconcentrate under reduced pressure