4-Fluorobenzoic Acid → HCID 22557753, compound

HRID 984066Notes

Reaction equation

HRID 984066 reaction equation
[CH3:1][C:2]1[N:3]([CH:8]2[CH2:13][CH2:12][NH:11][CH2:10][CH2:9]2)[C:4]([CH3:7])=[CH:5][CH:6]=1.F[C:15]1[CH:23]=[CH:22][C:18]([C:19]([OH:21])=[O:20])=[CH:17][CH:16]=1.C(N([CH:30]([CH3:32])[CH3:31])CC)(C)C.[C:33](=O)([O-])[O-].[K+].[K+]>C(OCC)(=O)C.O.CN(C)C=O>[CH3:1][C:2]1[N:3]([CH:8]2[CH2:13][CH2:12][N:11]([C:22]3[CH:23]=[CH:15][CH:16]=[CH:17][C:18]=3[C:19]([O:21][C:30]([CH3:32])([CH3:33])[CH3:31])=[O:20])[CH2:10][CH2:9]2)[C:4]([CH3:7])=[CH:5][CH:6]=1

Participants

8

Reactant 4

HCID 99734-Fluorobenzoic AcidHCID 11430Potassium CarbonateHCID 81531DiisopropylethylamineHCID 225577164-(2,5-Dimethyl-1H-pyrrol-1-yl)piperidine

Product 1

HCID 22557753HCID 22557753, compound

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
90 °C

Procedure

1.5 g (7.5 mmol) of 4-(2,5-dimethylpyrrol-1-yl)piperidine, 60 ml of dimethylformamide and 1.6 g (7.5 mmol) of the tert-butyl ester of 4-fluorobenzoic acid and 2.6 ml of diisopropylethylamine are mixed under nitrogen. The mixture is heated with stirring for 6 hours at 90° C. and afterwards is stirred at ambient temperature for 15 hours. 1.04 g (7.5 mmol) of potassium carbonate are added thereto and the mixture is heated at 90° C. for 5 days. The mixture is poured into water, extraction is carried out with ethyl acetate and washing is carried out with water. The two phases are separated, the organic phase is dried over sodium sulfate and filtered, and the solvent is evaporated under reduced pressure. Purification is carried out by chromatography on a column of silica gel, elution being carried out with a hexane/ethyl acetate=3/1 mixture. 4-(2,5-Dimethylpyrrol-1-yl)-1-(tert-butoxycarbonylphenyl)piperidine is isolated. 250 mg of NH2OH.HCl and 0.7 ml of ethanol are mixed under nitrogen and stirred for 30 minutes. 67 mg (1.2 mmol) of KOH in 0.3 ml of a 1/1 ethanol/water solution and 300 mg (0.084 mmol) of the above intermediate product in 0.5 ml of ethanol are added thereto. The mixture is heated at 80° C. for 12 hours. Extraction is carried out with ethyl acetate, KOH is added to the aqueous phase until a pH of 9 is achieved, and extraction is carried out with ethyl acetate. The two phases are separated, the organic phase is dried over sodium sulfate and filtered, and the solvent is evaporated under reduced pressure. The title compound is obtained.

Workup

  1. temperatureThe mixture is heated
  2. stirringafterwards is stirred at ambient temperature for 15 hours
  3. temperaturethe mixture is heated at 90° C. for 5 days
  4. washwashing
  5. customThe two phases are separated
  6. dry with materialthe organic phase is dried over sodium sulfate
  7. filtrationfiltered
  8. customthe solvent is evaporated under reduced pressure
  9. customPurification
  10. washis carried out by chromatography on a column of silica gel, elution

Sources & evidence

ORD record
ord-9e00241d5fbd47cd8151d400b8786890
Source dataset
uspto-grants-2005_03
Patent number
US06867220B2

Reaction notes

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