Water → 1-butylindole-3-carboxylic Acid

HRID 36035Notes

Reaction equation

HRID 36035 reaction equation
[OH-].[K+].[CH2:3]([N:7]1[C:15]2[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=2)[C:9]([C:16](=[O:21])C(F)(F)F)=[CH:8]1)[CH2:4][CH2:5][CH3:6].O.P(=O)(O)(O)[OH:24]>CO.C1(C)C=CC=CC=1.C(OCC)(=O)C>[CH2:3]([N:7]1[C:15]2[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=2)[C:9]([C:16]([OH:21])=[O:24])=[CH:8]1)[CH2:4][CH2:5][CH3:6]

Participants

8

Reactant 4

HCID 962WaterHCID 1004Phosphoric AcidHCID 14797Potassium HydroxideHCID 224017521-Butyl-3-trifluoroacetylindole

Product 1

HCID 103762901-butylindole-3-carboxylic Acid

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
50 °C

Procedure

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.

Workup

  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

Sources & evidence

ORD record
ord-d7ccb26d1f264b61a45ebaa58b5a8ce0
Source dataset
uspto-grants-1995_05
Patent number
US05412102

Reaction notes

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