反应详情

温度

65 °C

To the intermediate from Step A above (44.4 g, 185 mmol) in MeOH (16 mL) at rt was added sodium methoxide (13.98 g, 259 mmol). After stirring for 3 hours, acetic acid (42.3 mL, 739 mmol) and ammonium chloride (12.85 g, 240 mmol) were added to the reaction. The resulting slurry was heated to 65° C. and stirred for 4 hours. The reaction was then cooled to rt and quenched with EtOAc and saturated aqueous NaHCO3. The aqueous layer was removed and back extracted with EtOAc (4×). The combined organic layers were washed with 20% brine and dried over Na2SO4, filtered and the solvent removed under vacuum. EtOAc was added and the precipitated product was filtered and washed with methyl tert-butyl ether. The solid was dried at rt under vacuum oven overnight and the material used without further purification. 1H NMR (500 MHz, CH3OH-d4): δ 8.74 (d, J=4.57 Hz, 1H); 8.52 (d, J=8.32 Hz, 1H); 7.51 (dd, J=8.31, 4.44 Hz, 1H); 4.96 (t, J=6.91 Hz, 3H); 3.08-2.97 (m, 2H). m/z=258.3 (M+H).

1. stirringstirred for 4 hours
2. temperatureThe reaction was then cooled to rt
3. customquenched with EtOAc and saturated aqueous NaHCO3
4. customThe aqueous layer was removed
5. extractionback extracted with EtOAc (4×)
6. washThe combined organic layers were washed with 20% brine
7. dry with materialdried over Na2SO4
8. filtrationfiltered
9. customthe solvent removed under vacuum
10. additionEtOAc was added
11. filtrationthe precipitated product was filtered
12. washwashed with methyl tert-butyl ether
13. customThe solid was dried at rt under vacuum oven overnight
14. customthe material used without further purification