Cyclohexanone → 2-Cyclohexyl-3-oxo-3-(2-oxo-cyclohexyl)-propionic acid ethyl ester

HRID 1678616Notes

Reaction equation

HRID 1678616 reaction equation
[Li+].CC([N-]C(C)C)C.[C:9]1(=[O:15])[CH2:14][CH2:13][CH2:12][CH2:11][CH2:10]1.[CH2:16]([O:18][C:19](=[O:38])[CH:20]([CH:32]1[CH2:37][CH2:36][CH2:35][CH2:34][CH2:33]1)[C:21](N1C2C=CC=CC=2N=N1)=[O:22])[CH3:17]>C1COCC1>[CH2:16]([O:18][C:19](=[O:38])[CH:20]([CH:32]1[CH2:37][CH2:36][CH2:35][CH2:34][CH2:33]1)[C:21](=[O:22])[CH:10]1[CH2:11][CH2:12][CH2:13][CH2:14][C:9]1=[O:15])[CH3:17]

Participants

5

Reactant 3

HCID 7967CyclohexanoneHCID 2724682Lithium diisopropylamideHCID 3722282ethyl 3-(1H-benzotriazol-1-yl)-2-cyclohexyl-3-oxopropanoate

Product 1

HCID 671312392-Cyclohexyl-3-oxo-3-(2-oxo-cyclohexyl)-propionic acid ethyl esterYield 21%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
-78 °C

Procedure

To a −78° C. cold solution of LDA (2 M solution in heptane/ethylbenzene/THF, 1.8 ml, 3.66 mmol) in THF (16.8 ml) under an argon atmosphere was added a solution of cyclohexanone (380 μl, 3.66 mmol; CAS Reg. No. 108-94-1) in THF (12.6 ml) within 10 min. The mixture was stirred for 1 h at −78° C. A solution of 3-benzotriazol-1-yl-2-cyclohexyl-3-oxo-propionic acid ethyl ester (1.05 g, 3.33 mmol) in THF (11.1 ml) was added and the solution was stirred at ambient temperature for 14 h. Ice water was added, the mixture was poured onto ice water/brine 1/1 and extracted two times with TBME. The combined extracts were washed with ice water/brine 1/1 and dried over Na2SO4. After filtration the solvent was removed under reduced pressure to give a yellow oil which was purified by column chromatography (silica gel, iPrOAc/heptane) to give the title compound (209 mg, 0.71 mmol; 21%) as yellow oil. MS: m/e=295.2 [M+H+].

Workup

  1. stirringthe solution was stirred at ambient temperature for 14 h
  2. extractionextracted two times with TBME
  3. washThe combined extracts were washed with ice water/brine 1/1
  4. dry with materialdried over Na2SO4
  5. filtrationAfter filtration the solvent
  6. customwas removed under reduced pressure
  7. customto give a yellow oil which
  8. customwas purified by column chromatography (silica gel, iPrOAc/heptane)

Sources & evidence

ORD record
ord-9080364217704693a77758b21eb0c23a
Source dataset
uspto-grants-2011_08
Patent number
US08008505B2

Reaction notes

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