Chloromethyl Methyl Ether → 1-Tert-butyl 4-ethyl 4-(methoxymethyl)piperidine-1,4-dicarboxylate

Participants

Reaction Conditions

Reaction Steps

To a solution of 1-tert-butyl 4-ethyl piperidine-1,4-dicarboxylate (1.0 g, 4.07 mmol) in THF (20 mL) at −78° C. under nitrogen was added dropwise LDA (1.5 M in THF, 4.0 mL, 6.10 mmol). This solution was stirred for 1 hour at −78° C., after which methoxymethyl chloride (0.8 mL, 10.5 mmol) was added. The system was allowed to warm slowly to room temperature over 2 hours. The reaction was quenched with aqueous NH4Cl and extracted with ethyl acetate (3×50 mL). The organic layer was dried over a pad of silica gel, and the solvent removed under vacuum. The title compound was isolated by silica gel chromatography (5-10% ethyl acetate:hexanes) as a clear oil (830 mg, 69% yield). MS (ES+) [M+H]+=302.4.

Provenance & Evidence