反应详情

温度

35 °C

Acrylic acid (commercially available, for example, from Aldrich) (46 ml, 0.67 mol) was added slowly to a stirred suspension of 4-amino-5-chloro-2-methoxybenzaldehyde (Step B) (50.0 g, 0.27 mol) and triethylamine (204 g, 2.02 mol) in ethyl acetate (0.85 L) at 25° C. Propanephosphonic anhydride (50% in ethyl acetate; 429 g, 0.67 mol) was added over 30 minutes keeping reaction temperature at 30-40° C. The mixture was stirred at 30-40° C. for a further 1 hour and then cooled to 25° C. and diluted with water (0.26 L) and acidified with 32% hydrochloric acid (108 g) to pH 2-3. The organic layer was separated and washed with a mixture of water (0.23 L) and 32% sodium hydroxide (14 g)—aqueous layer ca. pH 7. The organic phase was washed with water (0.23 L) and then concentrated under reduced pressure (ca. 300 mbar) to remove 0.56 kg of distillate. Methylcyclohexane (335 g) was added and then a further 286 g of distillate was removed under reduced pressure. Methylcyclohexane (111 g) was added and then the resulting suspension was cooled to 20° C., filtered and washed with methylcyclohexane. The cake was dried at 40° C. under reduced pressure for 12 hours to give N-[2-chloro-4-formyl-5-(methyloxy)phenyl]-2-propenamide (46 g, 71%)

1. customreaction temperature at 30-40° C
2. temperaturecooled to 25° C.
3. customThe organic layer was separated
4. washwashed with a mixture of water (0.23 L) and 32% sodium hydroxide (14 g)—aqueous layer
5. washThe organic phase was washed with water (0.23 L)
6. concentrationconcentrated under reduced pressure (ca. 300 mbar)
7. customto remove 0.56 kg of distillate
8. additionMethylcyclohexane (335 g) was added
9. customa further 286 g of distillate was removed under reduced pressure
10. additionMethylcyclohexane (111 g) was added
11. temperaturethe resulting suspension was cooled to 20° C.
12. filtrationfiltered
13. washwashed with methylcyclohexane
14. customThe cake was dried at 40° C. under reduced pressure for 12 hours