反应详情

温度

78 °C

A stirred mixture of 2-fluoro-6-methoxybenzoic acid (2 g, 11.7 6 mmol) and hydrazinecarbothioamide (1.607 g, 17.63 mmol) was cooled under nitrogen atmosphere in an ice bath and POCl3 (3.29 mL, 35.3 mmol) was added drop-wise. On completion of the addition, the reaction mixture was stirred at 78° C. for 3 hours. The reaction mixture was cooled in an ice bath and quenched by addition of ice water (˜50 mL) to give a solid/gum-like mass. This solid was sonicated for 1.5 hours and the resulting suspension was diluted with a further 50 mL of water then slurried at room temperature for ˜16 hours. The solid was collected by vacuum filtration, rinsed with water, re-suspended in saturated NaHCO3(aq) (˜100 mL) and slurried for ˜30 minutes. The resulting solid was collected by vacuum filtration, then rinsed with water to afford the crude product as an off-white solid. The crude material was pre-absorbed onto silica gel and purified by flash chromatography using a 120 g silica cartridge with a 0-10% MeOH/DCM gradient as the eluent to afford the title compound as a pale yellow solid (1.265 g, 45% yield). LC-MS: Rt 0.77 min; MS m/z 226.1 [M+H]+ [Method A]. 1H NMR (400 MHz, DMSO-d6) δ ppm 7.48 (td, J=8.34, 6.57 Hz, 1H), 7.29 (s, 2H), 7.02 (d, J=8.08 Hz, 1H), 6.91-6.99 (m, 1H), 3.85 (s, 3H).

1. temperaturewas cooled under nitrogen atmosphere in an ice bath
2. additionOn completion of the addition
3. temperatureThe reaction mixture was cooled in an ice bath
4. customquenched by addition of ice water (˜50 mL)
5. customto give a solid/gum-like mass
6. customThis solid was sonicated for 1.5 hours
7. waitthen slurried at room temperature for ˜16 hours
8. filtrationThe solid was collected by vacuum filtration
9. washrinsed with water
10. waitslurried for ˜30 minutes
11. filtrationThe resulting solid was collected by vacuum filtration
12. washrinsed with water
13. customto afford the crude product as an off-white solid
14. customThe crude material was pre-absorbed onto silica gel
15. custompurified by flash chromatography