4-Methylmorpholine → 1,1-Dimethylethyl 4-(3-methyl-1,2,4-oxadiazol-5-yl)-1-piperidinecarboxylate

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Reaction Steps

1-(tert-Butoxycarbonyl)piperidine-4-carboxylic acid (5.00 g, 21.83 mmol), 1-hydroxybenzotriazole (2.95 g, 21.83 mmol) and N-methylmorpholine (4.8 mL, 43.67 mmol) were dissolved in dichloromethane (100 mL), under argon, and (3-dimethylaminopropyl)carbodiimide hydrochloride (4.60 g, 24.0 mmol) and N′-hydroxyethanimidamide (1.62 g, 21.83 mmol) were added. The mixture was stirred at room temperature overnight then water (50 mL) was added and the mixture stirred for 30 minutes. The organics were separated, dried and the solvent evaporated to give a yellow oil which was redissolved in 1,4-dioxane (100 mL) and heated to 100° C. for 3 hours, cooled and the solvent evaporated to give crude tert-butyl 4-(3-methyl-1,2,4-oxadiazol-5-yl)piperidine-1-carboxylate as a brown oil (5.74 g, 98.5%).

Provenance & Evidence