Hydrochloric Acid → 3-(1-Carboxycyclopentyl)-2(dibenzylaminomethyl)propanoic acid t-butyl ester

Participants

Reaction Conditions

Reaction Steps

To a stirred solution of diisopropylamine (14.98 g, 20.75 ml, 148 mmole) in dry tetrahydrofuran (250 ml) cooled to -30° C. under nitrogen, was added dropwise, n-butyl lithium (59.3 ml of a 2.5M solution, 148 mmole), keeping the temperature below -20° C. The reaction was stirred at -20° C. for 1 hour, then cooled to -30° C. and cyclopentanecarboxylic acid (8.05 g, 7.65 ml, 70.6 mmole) added dropwise in a small amount of dry tetrahydrofuran. The reaction mixture was stirred at 0° C. for two hours, during which time a white precipitate formed. The solution was then cooled to -70° C., and a solution of 2-(dibenzylaminomethyl)-propenoic acid t-butyl ester (23.8 g, 70.6 mmol) in dry tetrahydrofuran (35 ml) was added dropwise. The reaction was left overnight (below -40° C.), and then poured into iced hydrochloric acid (4.2 eq, final pH=2) and the product extracted into diethyl ether. The ether layer was washed with hydrochloric acid, water (2×), dried (Na2SO4) and evaporated to yield the crude product (40 g). This was chromatographed over silica gel (500 g) eluting with dichloromethane containing methanol (0 to 5%) to yield, on evaporation of the pure fractions, 3-(1-carboxycyclopentyl)-2(dibenzylaminomethyl)propanoic acid t-butyl ester as an oil (18.3 g, 57%). Found: C,74 38; H,8.41; N,2 91. C28H37NO4 requires C,74.47; H,8.26; N,3.10%.

Provenance & Evidence