反应详情

Cool a solution of 5-(tert-butyldimethylsilyloxy)-3-iodo-1H-indazole (387.00 g, 1.08 mol) in DCM (2.50 L) and THF (1.00 L) to 10° C. in a 10 L jacketed reactor vessel. To the resulting mixture add methanesulfonic acid (14.0 mL, 216.02 mmol), followed by 3,4-dihydro-2H-pyran (296 mL, 3.24 mol) over 0.5 hours, observing a slight exotherm. Stir the mixture at RT for 3 hours. Cool the reaction to 10° C. and quench with saturated aqueous sodium bicarbonate (2 L). Dilute the mixture with water (2 L) and extract the aqueous layer with DCM (2 L). Wash the combined organic extracts with water (2 L) and brine. Dry the organic mixture over anhydrous sodium sulfate, filter and concentrate in vacuo. Elute the residue through a silica gel pad with eluent (0 to 10% EA/hexanes) to give the title compound. Yield: 150 g (31%). MS (ES) m/z 459 [M+1]+.

1. temperatureCool
2. customthe reaction to 10° C.
3. customquench with saturated aqueous sodium bicarbonate (2 L)
4. additionDilute the mixture with water (2 L)
5. extractionextract the aqueous layer with DCM (2 L)
6. washWash the combined organic extracts with water (2 L) and brine
7. dry with materialDry the organic mixture over anhydrous sodium sulfate
8. filtrationfilter
9. concentrationconcentrate in vacuo
10. washElute the residue through a silica gel pad with eluent (0 to 10% EA/hexanes)