Hydrochloric Acid → HCID 178517913, compound

Participants

Reaction Conditions

Reaction Steps

Ethyl 1-benzyl-3-oxopiperidine-4-carboxylate (30 g, 101 mmol) was combined with formamidine aceate (10.5 g, 101 mmol) and EtOH (450 mL) in a 2-liter flask. The resulting mixture was stirred at 0° C. and treated with NaOEt (21% in EtOH) (112.6 mL, 299 mmol). The reaction was heated at 60° C. overnight and monitored for completion via 1 cms and TLC (DCM:MeOH:: 95:5). Additional ethyl 1-benzyl-3-oxopiperidine-4-carboxylate (2 g, 6.6 mmol) was added after 12 h with continued heating at 60° C. The reaction was complete after 4 h as indicated by LCMS. The cooled reaction was reduced in vacuo and the residue was treated concentrated HCl (300 mL) and stirred overnight at room temperature. The solvents were removed under vacuum and the resulting solids treated with EtOH (300 mL), stirred for 15 minutes, and then filtered. The mother liquor was discarded and the precipitate dried in a vacuum oven affording 7-benzyl-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-4-ol (44 g) as the tri-HCl salt which was used directly in the next step.

Provenance & Evidence