Lithium Hydroxide → 4-(Piperidin-1-yl)benzoic acid

HRID 336227Notes

Reaction equation

HRID 336227 reaction equation
F[C:2]1[CH:11]=[CH:10][C:5]([C:6]([O:8]C)=[O:7])=[CH:4][CH:3]=1.[NH:12]1[CH2:17][CH2:16][CH2:15][CH2:14][CH2:13]1.[OH-].[Li+].[OH-].[Na+]>CN(C=O)C.C1COCC1.O>[N:12]1([C:2]2[CH:11]=[CH:10][C:5]([C:6]([OH:8])=[O:7])=[CH:4][CH:3]=2)[CH2:17][CH2:16][CH2:15][CH2:14][CH2:13]1

Participants

8

Reactant 4

HCID 3939Lithium HydroxideHCID 8082PiperidineHCID 14798Sodium HydroxideHCID 67878Methyl 4-fluorobenzoate

Product 1

HCID 7645994-(Piperidin-1-yl)benzoic acid

Reagents, catalysts & solvents 3

HCID 962WaterSolvent2×HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
50 °C

Procedure

A mixture of methyl 4-fluorobenzoate (Lancaster 14154; 500 mg; 3.24 mmol; 1 eq.) and piperidine (Fluka 80640; 828.62 mg; 9.73 mmol; 3 eq.) in DMF (2 mL) was stirred at 50° C. for 16 hours. The reaction mixture was then passed through a short pad of silica and the obtained solution evaporated in vacuo to give a colourless oil. The oil was taken up in THF (15 mL) and lithium hydroxide (388.41 mg; 16.22 mmol; 5 eq.) was added followed by water (15 mL). The reaction mixture was stirred at room temperature for 6 hours then at 60° C. for 16 hours. NaOH (155.5 mg, 6.48 mmol, 2 eq) was then added and the reaction mixture was refluxed for 24 hours. After cooling, the solution was diluted with water and washed with Et2O. The aqueous layer was then acidified to pH 5-6 with acetic acid and the formed precipitate was collected by filtration, washed with water and dried under high vacuum to afford the title compound as a white solid.

Workup

  1. customthe obtained solution evaporated in vacuo
  2. customto give a colourless oil
  3. stirringThe reaction mixture was stirred at room temperature for 6 hours
  4. waitat 60° C. for 16 hours
  5. temperaturethe reaction mixture was refluxed for 24 hours
  6. temperatureAfter cooling
  7. washwashed with Et2O
  8. filtrationthe formed precipitate was collected by filtration
  9. washwashed with water
  10. customdried under high vacuum

Sources & evidence

ORD record
ord-2230f89093db4e649b0bbaea6606ee11
Source dataset
uspto-grants-2014_11
Patent number
US08889668B2

Reaction notes

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