反应详情

温度

40 °C

Triphosgene (217 mg, 0.73 mmol) was added to a solution of (R)-(−)-2-butanol (Aldrich Chemical Company, Inc., Milwaukee, Wis., USA 148 mg, 2 mmol) in a mixture of pyridine (190 μL, 2.3 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 (3 mL) were added. The layers were separated and the organic phase was dried (magnesium sulfate), filtered, and evaporated. 4-(4-Methanesulfonyl-phenoxy)-1-piperidin-4-yl-1H-pyrazolo[3,4-d]pyrimidine trifluoroacetate salt (Intermediate 27; 220 mg, 0.45 mmol) and diisopropylethylamine (250 μL) were added and the mixture was stirred for 30 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 (R)-sec-butyl ester (78 mg, 36%) as an off-white foam/solid.

1. temperaturecooled to room temperature
2. customThe layers were separated
3. dry with materialthe organic phase was dried (magnesium sulfate)
4. filtrationfiltered
5. customevaporated
6. stirringthe mixture was stirred for 30 min
7. customchromatographed
8. washeluting with 50-75% ethyl acetate/hexanes