反应详情

To a suspension of sodium hydride, 60% in mineral oil (207 mg, 5.17 mmol) in THF (20 mL) was added 4-methyltetrahydro-2H-pyran-4-ol (500 mg, 4.30 mmol) at 0° C. After stirring 30 min, the solution was transferred to a solution of di(pyridin-2-yl)carbonate (931 mg, 4.30 mmol) in THF (20 mL) through a cannula. The formed slurry was stirred at 0° C. for 30 min. The slurry was warmed to rt and stirred for 2 h. At room temperature, to the reaction mixture was added sat. aq. NH4Cl (1 mL) upon which brief and significant effervescence was observed. The mixture was transferred to a 250 mL separatory funnel and was diluted with Et2O (50 mL). The solution was washed with water:brine (25 mL: 25 mL). The aq. phase was extracted with EtOAc (100 mL). The combined organics were dried over MgSO4; filtered; then concentrated in vacuo. The resulting residue was dissolved in acetone and then concentrated onto Celite in vacuo. The resulting powder was subjected to SiO2 purification on the Biotage system [90 g SiO2 column, hexanes:EtOAc 90:10 to 60:40 over 8 CV] to get the product as a clear oil. 1H NMR (400 MHz, CHLOROFORM-d) δ 8.48-8.39 (m, 1H), 7.87-7.76 (m, 1H), 7.30-7.24 (m, 2H), 7.16-7.09 (m, 1H), 3.83-3.69 (m, 4H), 2.29-2.16 (m, 2H), 1.80 (ddd, J=14.3, 8.9, 5.9 Hz, 2H), 1.66 (s, 3H).

1. stirringThe formed slurry was stirred at 0° C. for 30 min
2. stirringstirred for 2 h
3. customThe mixture was transferred to a 250 mL separatory funnel
4. washThe solution was washed with water
5. extractionThe aq. phase was extracted with EtOAc (100 mL)
6. dry with materialThe combined organics were dried over MgSO4
7. filtrationfiltered
8. concentrationthen concentrated in vacuo
9. dissolutionThe resulting residue was dissolved in acetone
10. concentrationconcentrated onto Celite in vacuo
11. customThe resulting powder was subjected to SiO2 purification on the Biotage system [90 g SiO2 column, hexanes:EtOAc 90:10 to 60:40 over 8 CV]