反应详情

Diethyl azodicarboxylate (15.4 mL) was added to a 0° C., stirred slurry of (R)-2-methyl-4,4,4-trifluorobutan-1-ol (about 12.0 g), phthalimide (13.4 g), and triphenylphosphine (23.7 g) in diethyl ether (about 6.5 g, see above) and dry tetrahydrofuran (110 mL), warmed to room temperature overnight, and stirred an additional 8 h. The mixture was evaporated, methylene chloride was added to the residue, and the slurry was filtered. The filtrate was purified by flash chromatography, eluting with 1:1 methylene chloride:hexanes, to give (R)-2-(2-methyl-4,4,4-trifluorobutyl)-1H-isoindol-1,3(2H)-dione (17.1 g, 75%) as a white solid; mp 45°-47° C.; partial NMR (400 MHz, CDCl3): 1.08 (d, 3H, CH3), 1.94-2.07 (m, 1H, CF3CH2), 2.14-2.31 (m, 1H, CF3CH2), 2.36-2.50 (m, 1H, CHCH3), 3.58 (dd, 1H, CH2N), 3.64 (dd, 1H, CH2N).

1. customThe mixture was evaporated
2. additionmethylene chloride was added to the residue
3. filtrationthe slurry was filtered
4. customThe filtrate was purified by flash chromatography
5. washeluting with 1:1 methylene chloride