Hydrochloric Acid → 1-{2-[(Benzyloxy)carbonyl]-4-methoxybutyl}-cyclopentanecarboxylic acid

Participants

Reaction Conditions

Reaction Steps

n-Butyl lithium (2.5M in hexane, 18.16 ml, 45.4 mmole) was added dropwise under nitrogen to a stirred solution of diisopropylamine (4.59, 45.4 mmole) in dry tetrahydrofuran (20 ml) keeping the temperature between -40° and -20° C. Stirring was continued at -20° C. for half an hour and cyclopentane carboxylic acid (2.59 g, 22.7 mmole) in dry tetrahydrofuran (10 ml) was added over five minutes, keeping the temperature at -20° C. The mixture was allowed to attain room temperature over one and a half hours, stirred for a further one hour and then cooled to -73° C. 2-(2-Methoxyethyl)propenoic acid benzyl ester (5.0 g, 22.7 mmole) in dry tetrahydrofuran (10 ml) was added dropwise keeping the temperature below -70° C. After two hours at -77° C., the mixture was quickly warmed to 0° C., acidified with 5N hydrochloric acid, and extracted with hexane. The hexane extract was washed (×7) with a mixture of water and saturated aqueous sodium bicarbonate (1:1 by volume) to remove unreacted cyclopentane carboxylic acid. The extract was washed with water, dried (MgSO4) and evaporated under vacuum to give a pale yellow oil (6.3 g) which was chromatographed on silica gel (600 g). Gradient elution starting with a mixture of ethyl acetate and hexane (3:7 by volume) changing to neat ethyl acetate gave the required product as a colourless oil (4.0 g, 53%). Found: C,68.39 ; H,7.99. C19H26O5 requires C,68.24; H,7.84%. On prolonged standing the material solidified and when recrystallised from hexane gave a white solid, m.p. 41°-2° C.

Provenance & Evidence