反应详情

温度

50 °C

To a solution of N-[4-methoxy-3-(2-methyl-2H-pyrazol-3-yl)phenyl]-acetamide (25.0 kg) in N,N-dimethylacetamide (DMA, 140.5 kg) in a 400 L glass lined jacketed reactor with overhead stirring under nitrogen at 45 to 55° C. internal temperature N-bromosuccinimide (NBS, 19.0 kg) was charged in portions at such a rate as to maintain internal temperature to less than 55° C. The reaction mixture remained a solution at this dilution of DMA and internal temperature of 50.9° C. An “in process check” of the reaction mixture to determine reaction completion after at least 1 hr of stirring at 50° C. showed that the reaction mixture was substantially free of the starting material. Upon cooling of the reaction mixture to an internal temperature of 34° C. water (150 kg) was added in a controlled manner into the reactor to maintain an internal temperature between 40-55° C. A slight exotherm was observed during the reaction quench. The product slurry was then cooled to −5 to 5° C. and filtered through a corrosion resistant filter/dryer. The wetcake was re-slurried, washed with water (2×25 kg), and dried under full house vacuum (˜30 in Hg) with a jacket temperature of 65° C. producing N-[3-(4 bromo-2-methyl-2H-pyrazol-3-yl)-4-methoxy phenyl]-acetamide (31.6 kg, 100% purity by HPLC, 96.1% yield).

1. additionwas charged in portions at such a rate as
2. temperatureto maintain internal temperature to less than 55° C
3. customreaction completion after at least 1 hr
4. additionwas added in a controlled manner into the reactor
5. temperatureto maintain an internal temperature between 40-55° C
6. customquench
7. temperatureThe product slurry was then cooled to −5 to 5° C.
8. filtrationfiltered through a corrosion resistant filter/dryer
9. washwashed with water (2×25 kg)
10. customdried under full house vacuum (˜30 in Hg) with a jacket temperature of 65° C.