Ethanol → 7-(1-Benzyloxycarbonyl-4-piperidyl)-2-carboxyheptanoic acid

HRID 280985Notes

Reaction equation

HRID 280985 reaction equation
[CH2:1]([O:8][C:9]([N:11]1[CH2:16][CH2:15][CH:14]([CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH:22]([C:28]([O:30]CC)=[O:29])[C:23]([O:25]CC)=[O:24])[CH2:13][CH2:12]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(O)C.[OH-].[Na+]>O>[CH2:1]([O:8][C:9]([N:11]1[CH2:16][CH2:15][CH:14]([CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH:22]([C:23]([OH:25])=[O:24])[C:28]([OH:30])=[O:29])[CH2:13][CH2:12]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 702EthanolHCID 14798Sodium HydroxideHCID 20143677Ethyl 7-(1-benzyloxycarbonyl-4-piperidyl)-2-ethoxycarbonylheptanoate

Product 1

HCID 201436527-(1-Benzyloxycarbonyl-4-piperidyl)-2-carboxyheptanoic acid

Reagents, catalysts & solvents 1

HCID 962WaterSolvent2×

Procedure

To a solution of sodium (0.95 g) in ethanol (80 ml) are added diethyl malonate (7.2 g) and 5-(1-benzyloxycarbonyl-4-piperidyl)pentylp-toluenesulfonate (13.7 g). The mixture is refluxed for 2 hours with stirring. After the further addition of a mixture of sodium (0.25 g), ethanol (25 ml) and diethyl malonate (1.8 g), the reflux is continued for further 2 hours. After evaporation of ethanol, the residue is diluted with water (200 ml) and extracted with ethyl acetate (300 ml). The extract is dried over anhydrous magnesium sulfate and evaporated in vacuo to give ethyl 7-(1-benzyloxycarbonyl-4-piperidyl)-2-ethoxycarbonylheptanoate as an oil. To a mixture of this ester and ethanol (30 ml) is added dropwise a solution of sodium hydroxide (6 g) in water (50 ml). After the addition is complete, the mixture is diluted with water (150 ml) and extracted with a mixture of ether and petroleum ether (1:1, 150 ml). The aqueous layer is acidified with concentrated hydrochloric acid and extracted with ethyl acetate (300 ml). The organic extract is washed with water, dried over anhydrous magnesium sulfate and evaporated in vacuo to give 7-(1-benzyloxycarbonyl-4-piperidyl)-2-carboxyheptanoic acid as an oil. This acid is heated for 1 hour at 160°-165° C. with stirring. The resulting oil is purified by silica gel column chromatography using hexane-ethyl acetate (3:1-1:1) as an eluent to yield 7-(1-benzyloxycarbonyl-4-piperidyl)heptanoic acid (6.4 g) as a colorless oil.

Workup

  1. additionAfter the addition
  2. extractionextracted with a mixture of ether and petroleum ether (1:1, 150 ml)
  3. extractionextracted with ethyl acetate (300 ml)
  4. extractionThe organic extract
  5. washis washed with water
  6. dry with materialdried over anhydrous magnesium sulfate
  7. customevaporated in vacuo

Sources & evidence

ORD record
ord-83d983bd9cb5402eb44ef48d4791c7ba
Source dataset
uspto-grants-1986_05
Patent number
US04591458

Reaction notes

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