反应详情

A separate solution of N-methyl-N-(2-[4-hydroxyphenyl]ethyl) amine (A12) was prepared by mixing A12.HBr (100 g), triethylamine (360 mL) in methylene chloride (1000 mL). To this A12 solution was added slowly the above mentioned B13-Cl solution with agitation at room temperature. The reaction mixture was stirred for another one hr at room temperature after the addition was completed. The solid precipitate was removed by filtration and the filter cake was washed with methylene chloride. The combined methylene chloride solution was distilled until the pot temperature reached 55° C. To this residue, methanol (198 g) was added. The methanol of the resulted solution was removed by distillation until the pot temperature reached 70° C. The residue was cooled to room temperature and 15% NaOH/MeOH solution (460 mL) was added. The resulting solution was stirred at room temperature for 12 hr. The reaction mixture was acidified with 36% hydrochloric acid until the pH was between 3 and 5. The solution was set for distillation until the pot temperature reached 75° C. To the residue was added methylene chloride (200 mL) and 1N HCl (1500 mL) and stirred at 0° C. for 4 hr. The precipitate was collect by filtration to give 100 g (56% yield) of N-methyl-N-(2-[4-hydroxyphenyl]ethyl)-2-bromo-5-hydroxy-4-methoxy benzene carboxamide (C2).

1. additionby mixing A12
2. additionTo this A12 solution was added slowly the
3. customat room temperature
4. additionafter the addition
5. customThe solid precipitate was removed by filtration
6. washthe filter cake was washed with methylene chloride
7. distillationThe combined methylene chloride solution was distilled until the pot temperature
8. customreached 55° C
9. additionTo this residue, methanol (198 g) was added
10. customThe methanol of the resulted solution was removed by distillation until the pot temperature
11. customreached 70° C
12. temperatureThe residue was cooled to room temperature
13. addition15% NaOH/MeOH solution (460 mL) was added
14. stirringThe resulting solution was stirred at room temperature for 12 hr
15. distillationThe solution was set for distillation until the pot temperature
16. customreached 75° C
17. additionTo the residue was added methylene chloride (200 mL) and 1N HCl (1500 mL)
18. stirringstirred at 0° C. for 4 hr
19. filtrationThe precipitate was collect by filtration