p-Toluenesulfonic acid → 1-Cyclopentylpiperidine-4-carboxylic acid

HRID 639754Notes

Reaction equation

HRID 639754 reaction equation
[C:1]1([CH3:11])[CH:6]=[CH:5][C:4](S(O)(=O)=O)=CC=1.[NH:12]1[CH2:17][CH2:16][CH:15]([C:18]([O:20]CC)=[O:19])[CH2:14][CH2:13]1.C1(=O)CCCC1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].[OH-].[Na+]>C1COCC1.CCO.C(O)(=O)C>[CH:4]1([N:12]2[CH2:13][CH2:14][CH:15]([C:18]([OH:20])=[O:19])[CH2:16][CH2:17]2)[CH2:5][CH2:6][CH2:1][CH2:11]1

Participants

9

Reactant 5

HCID 6101p-Toluenesulfonic acidHCID 8452CyclopentanoneHCID 14798Sodium HydroxideHCID 70770Ethyl 4-piperidinecarboxylateHCID 5049666Sodium triacetoxyborohydride

Product 1

HCID 230047221-Cyclopentylpiperidine-4-carboxylic acid

Reagents, catalysts & solvents 3

HCID 176Acetic AcidSolventHCID 702EthanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

Catalytic quantities of p-toluenesulphonic acid (750 mg) and 12.5 ml of glacial acetic acid are added to a solution of ethyl piperidine-4-carboxylate (22.9 g, 145 mmol) and cyclopentanone (13.5 g, 160 mmol) in 400 ml of THF. After stirring at RT for 30 min, sodium triacetoxyborohydride (42 g, 190 mmol) is added in portions. The reaction mixture is stirred at RT for 15 h and, after evaporating, the residue is extracted by shaking with sodium carbonate solution and dichloromethane. The organic phase is dried, filtered and evaporated. Yield: 32 g of ethyl 1-cyclopentylpiperidine-4-carboxylate. The intermediate compound (1 g, 4.4 mmol) is then hydrolysed, in 10 ml of EtOH, at 80° C. for 15 h with 10 ml of NaOH (5 N). After having been cooled down, the reaction mixture is acidified and the resulting precipitate is filtered off.

Workup

  1. stirringThe reaction mixture is stirred at RT for 15 h
  2. customafter evaporating
  3. extractionthe residue is extracted
  4. stirringby shaking with sodium carbonate solution and dichloromethane
  5. customThe organic phase is dried
  6. filtrationfiltered
  7. customevaporated
  8. temperatureAfter having been cooled down
  9. filtrationthe resulting precipitate is filtered off

Sources & evidence

ORD record
ord-2c385a05beb34fa9a930c50c849b58ac
Source dataset
uspto-grants-2010_04
Patent number
US07691888B2

Reaction notes

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