Borane;tetrahydrofuran → 1-Boc-4-(hydroxymethyl)-4-methylpiperidine

Participants

Reaction Steps

To a 0° C. solution of 4-methyl-piperidine-1,4-dicarboxylic acid mono-tert-butyl ester (5 g, 20.6 mmol) in THF (70 mL) was added dropwise over 20 min BH3.THF (31 mL, 1 M solution in THF, 31 mmol). The resultant reaction was allowed to warm slowly to room temperature, stirred at room temperature overnight, stirred at reflux for 4.5 h, allowed to cool to room temperature, treated with additional BH3.THF (30 mL, 1 M solution in THF, 30 mmol), and stirred at room temperature overnight. The reaction was divided into two batches and each was quenched with saturated NaHCO3 and extracted with EtOAc and the organic phase was dried over Na2SO4 and concentrated. The crude product from one batch was purified by flash chromatography using 110 g of silica gel and 0-50% of 9.5:0.5 MeOH:conc NH4OH in CH2Cl2 as eluant to afford 2.4 g of 4-hydroxymethyl-4-methyl-piperidine-1-carboxylic acid tert-butyl ester as a colorless oil.

Provenance & Evidence