反应详情

To a solution of 21 (2.09 g, 0.05 mol) in anhydrous 1,2-dichloroethane (100 mL) at reflux was added 1-chloroethyl chloroformate (0.82 mL, 7.47 mmol) drop wise. The resulting solution was heated under reflux for 5 h and then cooled to room temperature. This was then washed 1 time with saturated bicarbonate solution, 1× with water and then organic layer was evaporated and the resulting carbamate (foamy white solid, almost quantitative yield) was dissolved immediately in methanol (100 mL) and then refluxed overnight. After cooling to room temperature, methanol was removed under reduced pressure and the residue was treated with saturated sodium bicarbonate solution. This was then extracted with 3:1, CH2Cl2/THF, and the combined organic extracts were washed once with water. Removal of solvent under reduced pressure afforded 2.01 g (99%) of 22 as a white foamy solid: LCMS (APCI): m/z 405.2 (M+H)+; 1H NMR (CDCl3, 300 MHz) δ 7.80-7.83 [m, 2H], 7.68-7.71 [m, 2H], 7.23-7.28 [m, 3H], 6.78-6.81 [m, 1H], 4.84 [m, 1H], 3.86 [s, 1H], 3.75-3.80 [m, 2H], 3.32 [t, J=12 Hz, 1H], 3.03-3.15 [m, 2H], 2.90 [br s, 1H], 2.61-2.67 [m, 1H], 2.45 [d, J=12 Hz, 1H], 2.27-2.31 [m, 1H], 1.83-1.93 [m, 2H], 1.64 [dd, J1=15 Hz, J2=6 Hz, 2H], 1.31-1.48 [m, 3H], 1.24 [s, 3H]; 13C NMR (CDCl3, 300 MHz) δ 167.5, 158.1, 147.0, 132.9, 131.1, 127.5, 122.1, 120.5, 114.7, 109.8, 67.0, 54.3, 53.2, 46.5, 43.5, 41.8, 35.2, 34.8, 33.9, 32.9, 29.4, 24.7, 24.1, 22.9.

1. temperatureThe resulting solution was heated
2. temperatureunder reflux for 5 h
3. washThis was then washed 1 time with saturated bicarbonate solution, 1× with water
4. customorganic layer was evaporated
5. dissolutionthe resulting carbamate (foamy white solid, almost quantitative yield) was dissolved immediately in methanol (100 mL)
6. temperaturerefluxed overnight
7. temperatureAfter cooling to room temperature
8. custommethanol was removed under reduced pressure
9. additionthe residue was treated with saturated sodium bicarbonate solution
10. extractionThis was then extracted with 3:1, CH2Cl2/THF
11. washthe combined organic extracts were washed once with water
12. customRemoval of solvent under reduced pressure