反应详情

温度

50 °C

A solution of potassium hydroxide (6.9 kg, 133.7 mol) in 14 mL of methanol was heated to reflux temperature and crude 1-butyl-3-trifluoroacetylindole (11.5 kg) in 35 L of toluene was added slowly. The mixture was heated under reflux for 60 minutes, cooled to approximately 50° C. and 80 L of water was added. The aqueous layer was separated and extracted with 30 L toluene. Phosphoric acid was then added to the aqueous layer until a pH of 7.16 was obtained. Ethyl acetate was then added, followed by additional phosphoric acid until a pH of 2.38 was obtained. The ethyl acetate layer was separated and washed twice with water (2×40 L). The ethyl acetate layer was filtered, heated to 83° C. and combined with 40 L of heptane at which point crystallization occured. The mixture distilled until the mixture heated to 89° C., after which the mixture was cooled slowly. A crystalline product was obtained and isolated by filtration. Drying under nitrogen gave 1-butylindole-3-carboxylic acid (6.64 kg, 30.6 mol), m.p. 124°-126° C.

1. additionwas added slowly
2. temperatureThe mixture was heated
3. temperatureunder reflux for 60 minutes
4. customThe aqueous layer was separated
5. extractionextracted with 30 L toluene
6. additionPhosphoric acid was then added to the aqueous layer until a pH of 7.16
7. customwas obtained
8. customwas obtained
9. customThe ethyl acetate layer was separated
10. washwashed twice with water (2×40 L)
11. filtrationThe ethyl acetate layer was filtered
12. temperatureheated to 83° C.
13. customcombined with 40 L of heptane at which point crystallization
14. distillationThe mixture distilled until the mixture
15. temperatureheated to 89° C.
16. temperatureafter which the mixture was cooled slowly
17. customA crystalline product was obtained
18. customisolated by filtration
19. customDrying under nitrogen