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 underreflux 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 of7.16 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 Lof heptane at which point crystallization occured. The mixture distilled until the mixture heated to 89° C., afterwhich 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 underreflux for 60 minutes
3. customThe aqueous layer was separated
4. extractionextracted with 30 L toluene
5. additionPhosphoric acid was then added to the aqueous layer until a pH of7.16
6. customwas obtained
7. customwas obtained
8. customThe ethyl acetate layer was separated
9. washwashed twice with water (2×40 L)
10. filtrationThe ethyl acetate layer was filtered
11. temperatureheated to 83° C.
12. customcombined with 40 Lof heptane at which point crystallization
13. distillationThe mixture distilled until the mixture
14. temperatureheated to 89° C., afterwhich the mixture
15. temperaturewas cooled slowly
16. customA crystalline product was obtained
17. customisolated by filtration
18. customDrying under nitrogen