Acetic Acid → 4-Benzyl-1-(tert-butoxycarbonyl)piperidine-4-carboxylic acid

HRID 2287420Notes

Reaction equation

HRID 2287420 reaction equation
C([O:3][C:4]([C:6]1([CH2:19][C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[CH2:11][CH2:10][N:9]([C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])[CH2:8][CH2:7]1)=[O:5])C.[OH-].[Na+].C(O)(=O)C>C(O)(C)C.C1COCC1.O>[C:15]([O:14][C:12]([N:9]1[CH2:10][CH2:11][C:6]([CH2:19][C:20]2[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=2)([C:4]([OH:5])=[O:3])[CH2:7][CH2:8]1)=[O:13])([CH3:18])([CH3:16])[CH3:17]

Participants

7

Reactant 3

HCID 176Acetic AcidHCID 14798Sodium HydroxideHCID 162182711-tert-Butyl 4-ethyl 4-benzylpiperidine-1,4-dicarboxylate

Product 1

HCID 121510204-Benzyl-1-(tert-butoxycarbonyl)piperidine-4-carboxylic acidYield 66.4%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 3776IsopropanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a stirring solution of 4-benzylpiperidine-1,4-dicarboxylic acid tert-butyl ester ethyl ester (31.6 mmol, 11.01 g) in isopropyl alcohol (50 mL) and THF (50 mL) was added 3N NaOH (63.4 mmol, 21.1 mL) and the biphasic solution was heated to reflux. The reaction was heated for 8h. and then left stirring at room temperature overnight. The reaction was then diluted with water (200 mL) and acidified to pH=4 with glacial acetic acid. The aqueous mixture was then extracted with ethyl acetate (2×500 mL). The organic layers were combined, washed with brine, dried over anhydrous sodium sulfate, and evaporated under reduced pressure. The resulting solid was triturated with diethyl ether to give 6.7g of a white solid.

Workup

  1. temperaturethe biphasic solution was heated to reflux
  2. temperatureThe reaction was heated for 8h.
  3. waitleft
  4. extractionThe aqueous mixture was then extracted with ethyl acetate (2×500 mL)
  5. washwashed with brine
  6. dry with materialdried over anhydrous sodium sulfate
  7. customevaporated under reduced pressure
  8. customThe resulting solid was triturated with diethyl ether

Sources & evidence

ORD record
ord-67bce80067e049fca4dcee52af935610
Source dataset
uspto-grants-2000_07
Patent number
US06083949

Reaction notes

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