反应详情

温度

0 °C

A solution of 2-trifluoromethyl-2-propanol (Aldrich Chemical Company, Inc., Milwaukee, Wis., USA; 500 mg, 3.91 mmol) in pyridine (347 μL) was added to a cooled (0° C.) solution of triphosgene (386 mg, 1.3 mmol) in diethyl ether (35 mL). The mixture was stirred overnight and then 1 M aqueous hydrochloric acid (4 mL) was added. The organic layer was separated and washed with brine, dried (magnesium sulfate), filtered, and evaporated. The resulting material was dissolved in tetrahydrofuran (5 mL) and the solution was cooled to 0° C. 4-(4-Methanesulfonyl-phenoxy)-1-piperidin-4-yl-1H-pyrazolo[3,4-d]pyrimidine trifluoroacetate salt (Intermediate 27; 210 mg, 0.43 mmol) and triethylamine (560 μL, 4 mmol) were added. The mixture was stirred for 30 min and then poured into saturated aqueous ammonium chloride solution and extracted three times with ethyl acetate. The combined organic extracts were washed with brine, dried (magnesium sulfate), filtered, evaporated, and purified by column chromatography, eluting with 50% ethyl acetate/hexanes, to give 4-[4-(4-methanesulfonyl-phenoxy)-pyrazolo[3,4-d]pyrimidin-1-yl]-piperidine-1-carboxylic acid 2,2,2-trifluoro-1,1-dimethyl-ethyl ester (20.5 mg, 10%).

1. customThe organic layer was separated
2. washwashed with brine
3. dry with materialdried (magnesium sulfate)
4. filtrationfiltered
5. customevaporated
6. dissolutionThe resulting material was dissolved in tetrahydrofuran (5 mL)
7. stirringThe mixture was stirred for 30 min
8. extractionextracted three times with ethyl acetate
9. washThe combined organic extracts were washed with brine
10. dry with materialdried (magnesium sulfate)
11. filtrationfiltered
12. customevaporated
13. custompurified by column chromatography
14. washeluting with 50% ethyl acetate/hexanes