Hydrochloric Acid → 1-Benzoylpiperidine-4-carboxylic acid

HRID 1068237Notes

Reaction equation

HRID 1068237 reaction equation
[NH:1]1[CH2:9][CH2:8][CH:4]([C:5]([OH:7])=[O:6])[CH2:3][CH2:2]1.[OH-].[Na+].[C:12](Cl)(=[O:19])[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1.Cl>O>[C:12]([N:1]1[CH2:9][CH2:8][CH:4]([C:5]([OH:7])=[O:6])[CH2:3][CH2:2]1)(=[O:19])[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 37734-Piperidinecarboxylic acidHCID 7412Benzoyl chlorideHCID 14798Sodium Hydroxide

Product 1

HCID 789351-Benzoylpiperidine-4-carboxylic acidYield 44.3%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

To a solution of 10 g of isonipecotic acid in 100 mL of H2O was added 31 mL of 5 N NaOH at 0° C. The reaction was warmed to room temperature and stirred for 0.5 hr. The reaction was again cooled to 0° C. and 11.97 g of benzoyl chloride was added. The reaction was then warmed to room temperature and stirred for 1.5 hr. Concentrated HCl was then added until a precipitate formed. The mixture was extracted with 3×150 mL of EtOAc and the combined organic layers were dried over MgSO4. The solvent was evaporated under reduced pressure and the residue was dissolved in CH2Cl2. Ether was then slowly added to precipitate the product which was filtered to give 8 g of the title compound. 1H NMR (500 MHz) 1.83 (m, 3H), 2.10 (m, 1H), 2.65 (m, 1H), 3.12 (m, 2H), 3.79 (m, 1H), 4.53 (m, 1H), 7.38 (m, 5H).

Workup

  1. temperatureThe reaction was again cooled to 0° C.
  2. temperatureThe reaction was then warmed to room temperature
  3. stirringstirred for 1.5 hr
  4. customformed
  5. extractionThe mixture was extracted with 3×150 mL of EtOAc
  6. dry with materialthe combined organic layers were dried over MgSO4
  7. customThe solvent was evaporated under reduced pressure
  8. dissolutionthe residue was dissolved in CH2Cl2
  9. additionEther was then slowly added
  10. customto precipitate the product which
  11. filtrationwas filtered

Sources & evidence

ORD record
ord-1a98b155209a450fadfc89b1f76f6721
Source dataset
uspto-grants-2001_06
Patent number
US06248755B1

Reaction notes

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