Hydrochloric Acid → 4-{N'-[2-(4-fluoro-phenyl)-acetyl]-N'-methyl-hydrazino}-piperidine-1-carboxylic acid tert-butyl ester

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Reaction Steps

To a stirred solution of (4-fluorophenyl)-acetic acid N-methyl-hydrazide, 8, (2 g, 11 mmol) in ethanol (20 mL) is added commercially available 4-oxo-piperidine-1-carboxylic acid tert-butyl ester (2.19 g, 11 mmol). The reaction mixture is refluxed for 30 minutes, then cooled to room temperature after which NaCNBH3 (1.04 g, 16,5 mmol) is added. The pH of the reaction mixture is adjusted to about 3 with concentrated HCl and the reaction mixture stirred for 3 hours at room temperature. The mixture is neutralized with saturated sodium bicarbonate and extracted three times with CH2Cl2. The combined organic layers are dried, filtered and concentrated in vacuo. Purification over silica (EtOAc) affords 3.7 g (93% yield) of the desired product. ESI/MS: 366.3 (M+H).

Provenance & Evidence