Hydrochloric Acid → 1-(2-Ethyl-butyl)-cyclohexanecarboxylic acid isopropyl ester

Participants

Reaction Conditions

Reaction Steps

To a solution of diisopropylamine (1.90 g, 18.75 mmol) in THF (9 mL) 1.6 M n-BuLi in hexane (10.6 mL, 16.9 mmol) was added with stirring over 20 min at −65° C. The suspension was warmed up to −40° C. and then added via a teflon tube over 20 min to a stirred solution of cyclohexanecarboxylic acid isopropyl ester (2.393 g, 14.1 mmol) in THF (20 mL) at −65° C. The resulting solution was stirred 0.5 h at −65° C., then 1-bromo-2-ethylbutane (3.249 g, 19.68 mmol) in THF (10 mL) was added at −65° C. over 15 min. The solution was stirred 1.5 h at −65° C. and then overnight without a cooling bath while slowly warming up to room temperature. At 5° C. ice-water (15 mL) was added, followed by 2N HCl (30 mL). The organic phase was diluted with ethyl acetate and washed with sat. aq. NaHCO3 and with aq. NaCl. The aqueous phases were extracted with ethyl acetate. The organic phases were combined, dried over sodium sulfate and concentrated. The crude product (3.5 g) was distilled at 55° C. (0.01 mbar) to give 2.9 g (81%) 1-(2-ethyl-butyl)-cyclohexanecarboxylic acid isopropyl ester as a colorless oil, purity 93% (GC area) (cyclohexanecarboxylic acid diisopropylamide as impurity: 0.9% in dist. product and 0.7% in crude product).

Provenance & Evidence