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

HRID 656699Notes

Reaction equation

HRID 656699 reaction equation
C1(NC2CCCCC2)CCCCC1.CCCCCC.[CH:20]([O:23][C:24]([CH:26]1[CH2:31][CH2:30][CH2:29][CH2:28][CH2:27]1)=[O:25])([CH3:22])[CH3:21].Br[CH2:33][CH:34]([CH2:37][CH3:38])[CH2:35][CH3:36].Cl>C1COCC1>[CH:20]([O:23][C:24]([C:26]1([CH2:33][CH:34]([CH2:37][CH3:38])[CH2:35][CH3:36])[CH2:31][CH2:30][CH2:29][CH2:28][CH2:27]1)=[O:25])([CH3:22])[CH3:21]

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 7582DicyclohexylamineHCID 8058HexaneHCID 77432Pentane, 3-(bromomethyl)-HCID 81039Cyclohexanecarboxylic acid, 1-methylethyl ester

Product 1

HCID 445486591-(2-Ethyl-butyl)-cyclohexanecarboxylic acid isopropyl esterYield 85%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

To a solution of dicyclohexylamine (14.24 g, 78.5 mmol) in THF (35 mL) 1.6 M n-BuLi in hexane (44.2 mL, 70.7 mmol) was added with stirring over 50 min at temperature between −20° C. and −15° C. The resulting orange suspension was stirred 10 min at −20° C. and then added via a teflon tube over 20 min to a stirred solution of cyclohexanecarboxylic acid isopropyl ester (10.0 g, 58.75 mmol) in THF (75 mL) at 0-2° C. To the resulting solution 1-bromo-2-ethylbutane (13.58 g, 82.25 mmol) in THF (37.5 mL) was added at 0° C. over 15 min. The solution was stirred overnight at 0° C. and for an other 3 h at room temperature. At 5° C. ice-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 (15.5 g) was distilled at 60° C. (0.05 mbar) to give 12.7 g (85%) 1-(2-ethyl-butyl)-cyclohexanecarboxylic acid isopropyl ester as colorless oil, purity 99.2% (GC area). 1H-NMR (CDCl3, 400 MHz): ppm 0.80 (t, 6H), 1.15-1.39 (m, 11H), 1.23 (d, 6H), 1.40 (d, 2H), 1.51-1.59 (m, 2H), 2.02-2.12 (m, 2H). 4.95-5.05 (m, 1H).

Workup

  1. stirringThe resulting orange suspension was stirred 10 min at −20° C.
  2. stirringThe solution was stirred overnight at 0° C. and for an other 3 h at room temperature
  3. filtrationThe white suspension was filtered
  4. washthe filter cake was washed with water and ethyl acetate
  5. washThe organic phase of the filtrate was washed 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 (15.5 g) was distilled at 60° C. (0.05 mbar)

Sources & evidence

ORD record
ord-21eebb1a4f5744ba9c902530bdc346c9
Source dataset
uspto-grants-2011_12
Patent number
US08071803B2

Reaction notes

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