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

Temperature

0 °C

To a solution of dicyclohexylamine (15.55 g, 85.77 mmol) in THF (90 mL) 1.6 M n-BuLi in hexane (48.0 mL, 76.8 mmol) was added with stirring over 50 min at temperature between −20° C. and −15° C. The orange suspension was stirred 10 min at −20° C. and then warmed up to 0° C. To this suspension a solution of cyclohexanecarboxylic acid ethyl ester (10.0 g, 64.0 mmol) in THF (30 mL) was added over 15 min at 0° C. The resulting solution was stirred 30 min at 0° C. then 1-bromo-2-ethylbutane (14.79 g, 89.6 mmol) in THF (37.5 mL) was added at the same temperature over 15 min. Stirring was continued 5 h at 0° C. and overnight at room temperature. At 5° C. cold water (25 mL) was added, followed by 2N HCl (60 mL). The white suspension was filtered and the filter cake was washed with water and ethyl acetate. The organic phase of the filtrate was 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 (16.0 g) was distilled at 60° C. (0.05 mbar) to give 12.1 g (79%) 1-(2-ethyl-butyl)-cyclohexanecarboxylic acid ethyl ester as colorless oil, purity 97% (GC area) (cyclohexanecarboxylic acid dicyclohexylamide as impurity: not detectable in distilled product and 0.7% in crude product).

1. stirringThe orange suspension was stirred 10 min at −20° C.
2. stirringThe resulting solution was stirred 30 min at 0° C.
3. stirringStirring
4. waitwas continued 5 h at 0° C. and overnight at room temperature
5. filtrationThe white suspension was filtered
6. washthe filter cake was washed with water and ethyl acetate
7. washThe organic phase of the filtrate was washed with sat. aq. NaHCO3 and with aq. NaCl
8. extractionThe aqueous phases were extracted with ethyl acetate
9. dry with materialdried over sodium sulfate
10. concentrationconcentrated
11. distillationThe crude product (16.0 g) was distilled at 60° C. (0.05 mbar)

ORD record

ord-dd0f3169aa2a439db8f7f96d85b49e3f

Source dataset

uspto-grants-2011_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08071803B2