4-Methyloxybenzyl chloride → 1-Tert-butyl 3-ethyl 3-(4-methylbenzyl)piperidine-1,3-dicarboxylate

Participants

Reaction Conditions

Reaction Steps

A solution of the product from STEP 1 (5.0 g, 19.5 mmol) in 20 ml THF was added to a solution of lithium diisopropylamine (11.7 ml, 23.4 mmol, 2M solution) in 25 ml THF dropwise at −20° C. The resulting mixture was stirred at 0° C. for 15 min and allowed to warm to room temperature. After 1 h, the reaction was cooled to −20° C. and treated, dropwise, with a solution of 4-methoxy-benzyl chloride (3.1 g, 19.5 mmol) in 20 ml THF. The resulting mixture was stirred at −10° C. for 1 h, and warmed to 35° C. After 1 h, the reaction was quenched with 25 ml saturated aqueous NH4Cl solution. The product was extracted with ethyl acetate (2×100 ml). The aqueous layer was extracted with ethyl acetate. The combined layers were were washed with H2O, brine, and then dried with Na2SO4, and concentrated. The residue was purified by chromatography (on silica gel, ethyl acetate/hexane=1/4) to yield a viscous oil in 5.2 g. The 1H NMR spectrum of the product was consistent for the proposed structure.

Provenance & Evidence