反应详情

To a stirred solution of Intermediate 107E (130 mg, 0.433 mmol) in ClCH2CH2Cl (3 mL) was added POCl3 (0.056 mL, 0.606 mmol) and Hunig's base (0.113 mL, 0.649 mmol). The reaction was stirred at rt for 30 min and then heated to 85° C. for 3 h. The reaction mixture was concentrated and the residue was diluted with EtOAc. The organic layer was washed with saturated NH4Cl, dried over MgSO4, filtered and concentrated. The crude product was purified by silica gel chromatography (24 g silica gel, eluted with EtOAc in hexanes) to yield the desired product (102 mg, 74%) as a white solid. LCMS Anal. Calc'd for C17H19ClN2O2 318.11, found [M+H] 319.2. 1H NMR (500 MHz, CDCl3) δ 7.23 (d, J=8.80 Hz, 2H), 6.90 (d, J=8.80 Hz, 2H), 3.97 (t, J=6.60 Hz, 2H), 2.05 (s, 2H), 1.74-1.82 (m, 2H), 1.69 (s, 3H), 1.46-1.55 (m, 2H), 0.99 (t, J=7.43 Hz, 3H).

1. temperatureheated to 85° C. for 3 h
2. concentrationThe reaction mixture was concentrated
3. additionthe residue was diluted with EtOAc
4. washThe organic layer was washed with saturated NH4Cl
5. dry with materialdried over MgSO4
6. filtrationfiltered
7. concentrationconcentrated
8. customThe crude product was purified by silica gel chromatography (24 g silica gel, eluted with EtOAc in hexanes)