Methanol → 2-(4-fluoroanilino)-4-(1-methyl-1H-indol-5-yl)benzoic acid

HRID 2191761Notes

Reaction equation

HRID 2191761 reaction equation
[F:1][C:2]1[CH:31]=[CH:30][C:5]([NH:6][C:7]2[CH:19]=[C:18]([C:20]3[CH:21]=[C:22]4[C:26](=[CH:27][CH:28]=3)[N:25]([CH3:29])[CH:24]=[CH:23]4)[CH:17]=[CH:16][C:8]=2[C:9]([O:11]C(C)(C)C)=[O:10])=[CH:4][CH:3]=1.O1CCOCC1.CO.[OH-].[Na+]>O.C1(C)C=CC=CC=1>[F:1][C:2]1[CH:31]=[CH:30][C:5]([NH:6][C:7]2[CH:19]=[C:18]([C:20]3[CH:21]=[C:22]4[C:26](=[CH:27][CH:28]=3)[N:25]([CH3:29])[CH:24]=[CH:23]4)[CH:17]=[CH:16][C:8]=2[C:9]([OH:11])=[O:10])=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 887MethanolHCID 14798Sodium Hydroxide5×HCID 312751,4-DioxaneHCID 68959326tert-butyl 2-(4-fluoroanilino)-4-(1-methyl-1H-indol-5-yl)benzoate

Product 1

HCID 576680192-(4-fluoroanilino)-4-(1-methyl-1H-indol-5-yl)benzoic acid

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 1140TolueneSolvent

Conditions

Temperature
50 °C

Procedure

To the obtained tert-butyl 2-(4-fluoroanilino)-4-(1-methyl-1H-indol-5-yl)benzoate were added dioxane 1.5 mL, methanol 1.5 mL and 2.0 mol/L sodium hydroxide aqueous solution 0.29 mL, and it was stirred at 50° C. for 2 hours. After the reaction mixture was cooled to room temperature, 2.0 mol/L sodium hydroxide aqueous solution 0.20 mL was added to it, and it was stirred at 55° C. for 1 hour and 30 minutes. Subsequently, 2.0 mol/L sodium hydroxide aqueous solution 0.29 mL was added, it was stirred at 55° C. for 1 hour and 20 minutes, 2.0 mol/L sodium hydroxide aqueous solution 0.29 mL was added, it was stirred at 55° C. for 1 hour, 2.0 mol/L sodium hydroxide aqueous solution 0.29 mL was added, and it was stirred at 55° C. for 1 hour. After the reaction mixture was cooled to room temperature, toluene and water were added to it. The water layer was separated and collected, it was adjusted to pH3.4 with 1.0 mol/L hydrochloric acid after washing with toluene, and ethyl acetate was added to it. The organic layer was separated and collected,dried over anhydrous magnesium sulfate after washing with saturated sodium chloride aqueous solution, and the solvent was removed under reduced pressure. Diisopropyl ether was added to the obtained residue, solid matter was filtrated to give 2-(4-fluoroanilino)-4-(1-methyl-1H-indol-5-yl)benzoic acid 37 mg of a pale yellow solid.

Workup

  1. temperatureAfter the reaction mixture was cooled to room temperature
  2. stirringwas stirred at 55° C. for 1 hour and 30 minutes
  3. stirringit was stirred at 55° C. for 1 hour and 20 minutes
  4. stirringit was stirred at 55° C. for 1 hour
  5. stirringit was stirred at 55° C. for 1 hour
  6. temperatureAfter the reaction mixture was cooled to room temperature
  7. customThe water layer was separated
  8. customcollected
  9. washafter washing with toluene, and ethyl acetate
  10. additionwas added to it
  11. customThe organic layer was separated
  12. washafter washing with saturated sodium chloride aqueous solution
  13. customthe solvent was removed under reduced pressure
  14. additionDiisopropyl ether was added to the obtained residue, solid matter
  15. filtrationwas filtrated

Sources & evidence

ORD record
ord-cc8370d9a09d45088b624108a5824c0d
Source dataset
uspto-grants-2012_12
Patent number
US08327467B2

Reaction notes

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