Hydrochloric Acid → HCID 66669012, compound

Participants

Reaction Steps

A solution of (R)-tert-butyl 4-(4-(3-(6-methoxypyridin-3-yl)-3-oxo-1-o-tolylpropyl)-phenyl)piperidine-1-carboxylate (260 mg, 505 μmol), hydrogen chloride solution (4.0 M in 1,4-dioxane, 3.03 mL, 12.1 mmol) and water (0.5 mL) was heated to 100° C., then after 90 min the reaction mixture was purged with argon and concentrated to afford (R)-5-(3-(4-(piperidin-4-yl)phenyl)-3-o-tolylpropanoyl)pyridin-2(1H)-one hydrochloride (272 mg, light yellow foam, MS (ESI+): m/z=: 401.4 [M+H]+). This was taken up in dichloromethane (4 mL) and N,N-dimethylformamide (0.4 mL), then after addition of N,N-diisopropylethylamine (326 mg, 2.53 mmol) and a solution of di-tert-butyl-dicarbonate (121 mg, 0.56 mmol) at 0° C. After 30 min the reaction mixture was partitioned between sat. aq. sodium hydrogencarbonate solution and ethyl acetate. The organic layer was washed with brine, dried over magnesium sulfate, and evaporated. Chromatography (SiO2; gradient ethyl acetate/heptane 1:1 to ethyl acetate) afforded the title compound (204 mg, 81%). Light yellow foam, MS (ESI+): m/z=: 501.1 [M+H]+.

Provenance & Evidence