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

Participants

Reaction Steps

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).

Provenance & Evidence