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

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Reaction Steps

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.

Provenance & Evidence