Methyl iodide → Ethyl 3-methyl-4-oxocyclohexane-1-carboxylate

HRID 626946Notes

Reaction equation

HRID 626946 reaction equation
C[Si](C)(C)[N-][Si](C)(C)C.[Li+].[O:11]=[C:12]1[CH2:17][CH2:16][CH:15]([C:18]([O:20][CH2:21][CH3:22])=[O:19])[CH2:14][CH2:13]1.I[CH3:24]>C1COCC1.C(C1C=CC=CC=1)C.C1COCC1>[CH3:24][CH:13]1[C:12](=[O:11])[CH2:17][CH2:16][CH:15]([C:18]([O:20][CH2:21][CH3:22])=[O:19])[CH2:14]1

Participants

6

Reactant 3

HCID 6328Methyl iodideHCID 317638Ethyl 4-oxocyclohexanecarboxylateHCID 2733832Lithium Hexamethyldisilazide

Product 1

HCID 57465910Ethyl 3-methyl-4-oxocyclohexane-1-carboxylateYield 15%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 68569164HCID 68569164, compoundSolvent

Procedure

Lithium hexamethyldisilazanide in THF/ethylbenzene (1M, 117.5 mL) was added dropwise to a stirred solution of ethyl 4-oxocyclohexane-1-carboxylate (20 g, 0.12 mol) in THF (100 mL) at −78° C. The mixture was stirred for 30 minutes. Iodomethane (7.32 mL, 0.12 mol) was added dropwise, then the mixture was gradually warmed to room temperature over 1 h and stirred for 4 h. The mixture was quenched with water (200 mL) and extracted with ethyl acetate (2×200 mL). The combined organic layers were washed with brine (100 mL), dried over magnesium sulfate and concentrated under reduced pressure. The residue was purified twice by FCC, eluting with 20-70% ethyl acetate in cyclohexane, to afford the title compound (3.3 g, 15%) as a colourless oil. δH (500 MHz, CDCl3) 4.15 (q, J 7.1 Hz, 2H), 2.82 (tt, J 12.2, 3.5 Hz, 1H), 2.50-2.40 (m, 2H), 2.40-2.27 (m, 3H), 1.91-1.78 (m, 1H), 1.59 (q, J 13.0 Hz, 1H), 1.27 (t, J 7.1 Hz, 3H), 1.05 (d, J 6.5 Hz, 3H).

Workup

  1. stirringstirred for 4 h
  2. customThe mixture was quenched with water (200 mL)
  3. extractionextracted with ethyl acetate (2×200 mL)
  4. washThe combined organic layers were washed with brine (100 mL)
  5. dry with materialdried over magnesium sulfate
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified twice by FCC
  8. washeluting with 20-70% ethyl acetate in cyclohexane

Sources & evidence

ORD record
ord-006469f4b3d04dc2868dd27377410420
Source dataset
uspto-grants-2016_04
Patent number
US09309243B2

Reaction notes

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