Isopropyl chloroformate → 4-Hydrazino-piperidine-1-carboxylic acid isopropyl ester hydrochloride

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Reaction Steps

Triethylamine (8.35 g, 60 mmol) was added to a mixture of 4-oxopiperidine hydrate hydrochloride (4.61 g, 30 mmol) and tetrahydrofuran (200 mL) and the resulting poorly soluble mixture was stirred for 1 h. Isopropyl chloroformate (3.3 mL, 34.7 mmol) was added and the mixture was stirred overnight and then filtered. The solvent was evaporated to give a crude intermediate which was dissolved in methanol (80 mL). tert-Butyl carbazate (26 mmol) was added and the mixture was stirred for 2 h. Volatiles were evaporated to give an oil which was dissolved in 50% aqueous acetic acid (80 mL). Sodium cyanoborohydride (35 mmol) was added and the mixture was stirred for 3 h. The reaction mixture was neutralized with 3 M aqueous sodium hydroxide and then extracted three times with dichloromethane. The combined organic extracts were dried, filtered, and evaporated. HCl in dioxane (4 M; 25 mL) and methanol (20 mL) were added and the mixture was stirred for 1 h. Volatiles were evaporated to give 4-hydrazino-piperidine-1-carboxylic acid isopropyl ester hydrochloride (4.02 g, 56%) as a white solid.

Provenance & Evidence