反应详情

温度

77.5 °C

Into a reactor was added 5 (29.8 kg, 104 mol) and water (475 L). The mixture was heated to 75 to 80° C. and concentrated HCl (107 kg, 1051 mol) was added over a minimum of 30 min while maintaining the temperature between 75 and 80° C. The reaction mixture was stirred for 3 h at 75 to 80° C. The reaction mixture was sampled and the % conversion was determined by HPLC analysis. The mixture was heated at 75 to 80° C. until the % conversion reached >97.3% or until at total reaction time of 7 h. The reaction was cooled to 20 to 25° C. over a minimum of 3 h and stirred for an additional 2 h at 20 to 25° C. The reaction was filtered and washed with 16% w/w HCl (2×35 kg), water (82 L) and heptane (2×120 L). The resulting wet cake was dried under vacuum at 35 to 50° C. to provide 23.9 kg (93% yield) of 6. 1H NMR (300 MHz, DMSO-d6) δ 10.25 (s, 1H), 7.72 (s, 4H), 7.69 (d, J=8.8 Hz, 1H), 6.93 (d, J=2.3 Hz, 1H), 6.81 (dd, J=2.3, 8.8 Hz, 1H), 3.80 (s, 3H); MS (ESI) m/z 210.4 (M+, 100%).

1. temperaturewhile maintaining the temperature between 75 and 80° C
2. aliquotThe reaction mixture was sampled
3. temperatureThe mixture was heated at 75 to 80° C. until the % conversion
4. customuntil at total reaction time of 7 h
5. temperatureThe reaction was cooled to 20 to 25° C. over a minimum of 3 h
6. stirringstirred for an additional 2 h at 20 to 25° C
7. filtrationThe reaction was filtered
8. washwashed with 16% w/w HCl (2×35 kg), water (82 L) and heptane (2×120 L)
9. customThe resulting wet cake was dried under vacuum at 35 to 50° C.