反应详情

温度

40 °C

Triphosgene (208 mg, 0.7 mmol) was added to a solution of 1,3-difluoro-2-propanol (Aldrich Chemical Company, Inc., Milwaukee, Wis., USA 192 mg, 2 mmol) in a mixture of pyridine (2.2 mmol) and 1,2-dichloroethane (10 mL). The solution was stirred at 40° C. for 3 h and then cooled to room temperature. 1 M aqueous hydrochloric acid (2.5 mL) and water (5 mL) were added. The aqueous layer was extracted with dichloromethane and the combined organic layers were dried (magnesium sulfate), filtered, and evaporated. 4-(4-Methanesulfonyl-phenoxy)-1-piperidin-4-yl-1H-pyrazolo[3,4-d]pyrimidine trifluoroacetate salt (Intermediate 27; 200 mg, 0.41 mmol) and diisopropylethylamine (350 μL) were added and the mixture was stirred for 15 min and then chromatographed, eluting with 50-75% ethyl acetate/hexanes, to give 4-[4-(4-methanesulfonyl-phenoxy)-pyrazolo[3,4-d]pyrimidin-1-yl]-piperidine-1-carboxylic acid 2-fluoro-1-fluoromethyl-ethyl ester (64 mg, 32%) as a foamy solid.

1. temperaturecooled to room temperature
2. extractionThe aqueous layer was extracted with dichloromethane
3. dry with materialthe combined organic layers were dried (magnesium sulfate)
4. filtrationfiltered
5. customevaporated
6. stirringthe mixture was stirred for 15 min
7. customchromatographed
8. washeluting with 50-75% ethyl acetate/hexanes