Acetanilide → 3-Acetamido-4-chlorocinnamic acid

温度

45 °C

Tin II chloride dihydrate (103 g, 0.46 mol) was dissolved in concentrated HCl (120 mL). Warming was necessary to obtain a clear solution. 4-Chloro-3-nitrocinnamic acid (25 g, 0.11 mol) was added portionwise with stirring. After about 20% of the starting material had been added, the mixture was warmed with a heat gun to 45° C. to initiate reaction. The rate of addition was controlled to maintain a temperature of 65-75° C. Cooling with a water bath was used to prevent the temperature exceeding 80° C. After the addition was complete and reaction started to subside, the mixture was transferred to an oil bath at 65° C. for 1 h. The mixture was cooled to room temperature. The solid was filtered, washed with 2 M HCl, (60 mL) and sucked dry. The filter cake was dried in a vacuum oven for 1 h, then in air overnight, to give about 34 g crude product. This material was suspended in acetic acid (100 mL) with stirring and acetic anhydride (100 mL, 1.1 mol) was added in one portion. The temperature rose to 35° C. After the initial exotherm subsided, the mixture was stirred in an oil bath at 110° C. for 2 h, but did not dissolve. LCMS showed complete conversion to the desired acetanilide. The solution was cooled and water (50 mL) was added cautiously. The mixture was concentrated to about 200 mL. More water (100 mL) and 2 M HCl (50 mL) were added. The precipitate was filtered, washed with water and dried to give 3-acetamido-4-chlorocinnamic acid (25.0 g, 95%).

1. temperatureWarming
2. customto obtain a clear solution
3. customreaction
4. additionThe rate of addition
5. temperatureto maintain a temperature of 65-75° C
6. temperatureCooling with a water bath
7. customexceeding 80° C
8. additionAfter the addition
9. customreaction
10. temperatureThe mixture was cooled to room temperature
11. filtrationThe solid was filtered
12. washwashed with 2 M HCl, (60 mL)
13. customsucked dry
14. customThe filter cake was dried in a vacuum oven for 1 h
15. customin air overnight, to give about 34 g crude product
16. stirringwith stirring
17. customrose to 35° C
18. stirringthe mixture was stirred in an oil bath at 110° C. for 2 h
19. dissolutiondid not dissolve
20. temperatureThe solution was cooled
21. concentrationThe mixture was concentrated to about 200 mL
22. additionMore water (100 mL) and 2 M HCl (50 mL) were added
23. filtrationThe precipitate was filtered
24. washwashed with water
25. customdried

ORDレコード

ord-667423f988474931bbe12a074caff50d

出典データセット

uspto-grants-2014_08

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US08809326B2