Diisopropylamine → 1-(4-Benzyloxy-2-tert-butoxycarbonylbutyl)cyclohex-2-ene carboxylic acid

Participants

Reaction Conditions

Reaction Steps

To a solution of diisopropylamine (8.8 mL, 62.8 mmol) in dry tetrahydrofuran (140 mL) at -50° C. was added a 2.5M solution of n-butyllithium in hexane (25 mL, 12.5 mmol). The mixture was stirred at a temperature from -50° C. to -20° C. over 30 minutes and then cooled again to -50° C. Solid 1-cyclohexene carboxylic acid (3.75 g, 29.7 mmol) was added and the resulting mixture was allowed to warm to room temperature with stirring over 1.5 hours. The reaction was cooled to -78° C. and a solution of 2-(2-benzyloxyethyl)acrylic acid tert-butyl ester (7.45 g, 28.4 mmol) in dry tetrahydrofuran (90 mL) was added over 15 minutes; stirring was continued at -78° C. for 5 hours. The mixture was then allowed to warm to -30° C. over 40 minutes and was quenched by the addition of saturated aqueous NH4Cl solution. After acidification using 3N HCl solution, the mixture was extracted with ether. The extract was washed with brine, dried over MgSO4 and evaporated under vacuum to leave a yellow oil from which 1-(4-benzyloxy-2-tert-butoxycarbonylbutyl)cyclohex-2-ene carboxylic acid (an oily mixture of the two diastereomers), 9.71 g (84%) was isolated by chromatography on silica gel eluting with methylene chloride and then 5% methanol in methylene chloride.

Provenance & Evidence