Methyl chloroformate → 1-tert-Butyl 4-methyl 4-(hydroxymethyl)piperidine-1,4-dicarboxylate

Participants

Reaction Conditions

Reaction Steps

To a solution of 1-(tert-butoxycarbonyl)-4-(methoxycarbonyl)piperidine-4-carboxylic acid (6 g, 21 mmol) and DIEA (7.3 mL, 42 mmol, 2.0 equiv.) in THF (60 mL) was added methyl chloroformate (1.94 mL, 25 mmol, 1.2 equiv.) at 0° C. The mixture was stirred at 0° C. until the reaction was complete. NaBH4 (3.16 g, 84 mmol, 4.0 equiv.) was added at 0° C. MeOH (10 mL) was then added. The mixture was stirred at 0° C. for 90 min. The reaction mixture was then quenched by saturated NaHCO3 and concentrated to dryness. The residue was dissolved in ethyl acetate, washed with saturated NaHCO3, water and brine, dried over Na2SO4, and concentrated. The resulting residue was purified by column chromatography to give 1-tert-butyl 4-methyl 4-(hydroxymethyl)piperidine-1,4-dicarboxylate (2.6 g, 46%). LRMS (M-Boc+H+) m/z 174.1.

Provenance & Evidence