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

Temperature

-65 °C

To a solution of diisopropylamine (2.37 g, 23.4 mmol) in THF (12 mL) 1.6 M n-BuLi in hexane (13.2 mL, 21.09 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 15 min to a stirred solution of cyclohexanecarboxylic acid methyl ester (2.0 g, 14.1 mmol) in THF (20 mL) at −65° C. The resulting yellow solution was stirred 10 min at −65° C., then it was added over 30 min to a solution of 1-bromo-2-ethylbutane (3.714 g, 22.5 mmol) in THF (10 mL) at 0° C. The solution was stirred 1 h at 0° C. and then overnight without a cooling bath while 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 (3.3 g) was distilled at 45° C. (0.01 mbar) to give 2.1 g (66%) 1-(2-ethyl-butyl)-cyclohexanecarboxylic acid methyl ester as a colorless oil, purity 92.5% (GC area). The structure of the title compound was confirmed by GC-MS (M=226).

1. temperatureThe suspension was warmed up to −40° C.
2. stirringThe resulting yellow solution was stirred 10 min at −65° C.
3. stirringThe solution was stirred 1 h at 0° C.
4. temperatureovernight without a cooling bath while warming up to room temperature
5. washwashed with sat. aq. NaHCO3 and with aq. NaCl
6. extractionThe aqueous phases were extracted with ethyl acetate
7. dry with materialdried over sodium sulfate
8. concentrationconcentrated
9. distillationThe crude product (3.3 g) was distilled at 45° C. (0.01 mbar)

ORD record

ord-e4a3a3880ed147358c29ae5e332ba8e1

Source dataset

uspto-grants-2011_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08071803B2