Water → Ethyl 1-(1-benzylpiperidin-4-yl)cyclopropane carboxylate

HRID 1059334Notes

Reaction equation

HRID 1059334 reaction equation
[CH2:1]([N:8]1[CH2:13][CH2:12][CH:11]([CH:14]([CH2:20][CH2:21]Br)[C:15]([O:17][CH2:18][CH3:19])=[O:16])[CH2:10][CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(O[K])(C)(C)C.O.C(OCC)(=O)C>O1CCCC1>[CH2:1]([N:8]1[CH2:13][CH2:12][CH:11]([C:14]2([C:15]([O:17][CH2:18][CH3:19])=[O:16])[CH2:21][CH2:20]2)[CH2:10][CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 962WaterHCID 8857Ethyl AcetateHCID 18670444HCID 18670444, compoundHCID 178418922HCID 178418922, compound

Product 1

HCID 18670122Ethyl 1-(1-benzylpiperidin-4-yl)cyclopropane carboxylateYield 73.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

13 ml of diisopropylamine was dissolved in a solvent mixture of tetrahydrofuran (140 ml) with HMPA (15 ml) in a nitrogen atmosphere and cooled to −78° C. Into the obtained solution was dropped 42 ml of a 2.5 M solution of n-butyllithium in hexane and the resulting mixture was stirred at 0° C. for 30 minutes. After cooling to −78° C. again, 15 ml of a solution of 5.8 g of ethyl (1-benzylpiperidin-4-yl)acetate in tetrahydrofuran was dropped thereinto. The reaction mixture was stirred at 0° C. for 1 hour. Then 1,2-dibromoethane was dropped thereinto at −78° C. again. The reaction mixture was stirred at 0° C. for 30 minutes and then brought back to room temperature. Next, it was distributed into water and ethyl acetate. The organic layer was extracted, washed with water and dried over magnesium sulfate. After distilling off the solvent under reduced pressure, the residue was purified by silica gel column chromatography (eluted with n-hexane/ethyl acetate) to thereby give 1.40 g of ethyl 2-(1-benzyl-4-piperidyl)-4-bromobutanoate as a colorless oily substance. A solution of 1.40 g of ethyl 2-(1-benzyl-4-piperidyl)-4-bromobutanoate in tetrahydrofuran (20 ml) was stirred at room temperature and 1.0 g of t-butoxypotassium was added thereto. The reaction mixture was distributed into water and ethyl acetate. The organic layer was extracted and washed with water. After distilling off the solvent under reduced pressure, the obtained residue was purified by silica gel column chromatography (eluted with n-hexane/ethyl acetate) to thereby give 800 mg of the title compound as a colorless oily substance.

Workup

  1. extractionThe organic layer was extracted
  2. washwashed with water
  3. distillationAfter distilling off the solvent under reduced pressure
  4. customthe obtained residue was purified by silica gel column chromatography (eluted with n-hexane/ethyl acetate)

Sources & evidence

ORD record
ord-8ce6e00ecbbd46e3888b1ec3c17f91b9
Source dataset
uspto-grants-2003_02
Patent number
US06518423B1

Reaction notes

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