Benzyl chloroformate → Benzyl 3-hydroxy-4-(hydroxymethyl)piperidine-1-carboxylate

Participants

Reaction Steps

A solution of the 1-benzyl-4-hydroxymethyl-piperidin-3-ol from Step 1 above (13.5 g) in methanol (450 mL) was hydrogenated at 50 psi over 20% palladium hydroxide on charcoal (10 g) for 48 h in three batches. The combined reaction mixtures were filtered and the filtrate evaporated to give an oil. This was dissolved in water (100 mL) and dioxane (100 mL), cooled to 5° C., and benzyl chloroformate (7.8 mL) was added slowly, with addition of 1M NaOH to maintain a pH of 10–11. After 30 min, the cooling bath was removed and reaction mixture stirred for 30 min. The reaction mixture was concentrated to remove dioxane and the residue extracted with EtOAc (×3). The combined extracts were washed with brine, dried over anhydrous sodium sulfate and solvent evaporated to give a mixture of cis and trans 3-hydroxy-4-hydroxymethyl-piperidine-1-carboxylic acid benzyl ester products. Purification by flash column chromatography (80% EtOAc hexane to 5% MeOH EtOAc) gave the upper Rf cis isomer (major) and the lower Rf trans isomer (minor).

Provenance & Evidence