Ammonia → HCID 23447505, compound

Participants

Reaction Steps

A mixture of methyl 1-acetyl-4-cyanoisonipecotate (3.95 g), Raney nickel (3 g), concentrated ammonia solution (15 ml) and methanol (100 ml) was stirred at 5 atms under hydrogen atmosphere for 2 hours, and the catalyst was filtered off. The reaction solution was concentrated to give light blue oil of methyl 1-acetyl-4-aminomethylisonipecotate. To a solution of the obtained methyl 1-acetyl-4-aminomethylisonipecotate and N-(2,2-diethoxyethyl)-Z-glycine (6.12 g) in acetonitrile (100 ml) was added WSC (6.12 g), and the mixture was stirred at room temperature for 15 hours. The reaction solution was concentrated, and to the residue were added ethyl acetate and water. The separated organic layer was washed with water, sodium bicarbonate solution, citric acid solution and brine, dried and concentrated, and the residue was dissolved in toluene (100 ml). To the solution was added p-toluene sulfonic acid hydrate (164 mg), and the mixture was stirred at 100° C. for 30 minutes. The reaction solution was washed with saturated sodium bicarbonate solution and brine, dried and concentrated, and the residue was purified with silica gel column chromatography (ethyl acetate: methanol=50:1) to give colorless oil of 1-(1-acetyl-4-methoxycarbonylpiperidin-4-ylmethyl)-4-benzyloxycarbonyl-2-oxo-1,2,3,4-tetrahydropyrazine (2.4 g).

Provenance & Evidence