Sodium hydride → Methyl 2-(1-methylpiperidin-4-yl)acetate

Participants

Reaction Conditions

Reaction Steps

Methyl diethylphosphonoacetate (88.69 g, 0.422 mol) was added dropwise to a stirred suspension of sodium hydride (18.56 g, 60% dispersion in oil, 0.464 mol) in THF (300 ml) under nitrogen, at such a rate as to maintain the temperature below 30° C. The mixture was stirred for 1 h and a solution of N-methyl-4-piperidinone (47.71 g, 0.422 mol) in THF (150 ml) was added dropwise. The mixture was heated at 60° C. for 4.5 h before removing the solvent under vacuum and redissolving the residue in dichloromethane (300 ml) and water (200 ml). The dichloromethane phase was separated, washed successively with water (200 ml) and saturated sodium bisulphite solution (2×70 ml) and dried (MgSO4). The crude product was chromategraphed on silica gel, eluting with methanol/ether (5:95) to give the title-product (19.75 g, 28%). 1H NMR (250 MHz, CDCl3) δ (3H, s, N-CH3), 2.35 (2H, t, J=6 Hz, CH2), 2.40-2.50 (4H, m, 2 of CH2), 3.00 (2H, t, J=6 Hz, CH2), 3.70 (3H, s, CO2CH3), 5.65 (1H, s, vinyl CH).

Provenance & Evidence