Water → tert-Butyl 8-methyl-2-oxo-1,5,7,8-tetrahydro-1,6-naphthyridine-6(2H)-carboxylate

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Reaction Steps

tert-Butyl 3-methyl-4-oxopiperidine-1-carboxylate (commercially available from Ryan Scientific, Mt. Pleasant, S.C.)(1.7 g, 7.97 mmol) and pyrrolidine (1.3 mL, 15.94 mmol) were dissolved in toluene (9 mL), and the solution was heated under reflux, with the removal of water under Dean-Stark conditions, for 5 hours. The solution was then cooled to room temperature and propiolamide (prepared as described in EP 1813606)(1.1 g, 15.94 mmol) was added. The reaction mixture thus obtained was heated overnight under reflux. The reaction mixture was concentrated, and the residue was purified by flash chromatography on silica gel eluting with 0% to 10% MeOH in DCM to give the title compound (2.1 g, 55% yield). 1H NMR (400 MHz, CDCl3) δ ppm 1.36 (3H, d, J=7.04 Hz), 1.52 (9H, s), 3.37-3.44 (1H, m), 3.77-3.84 (1H, m), 4.12-4.17 (1H, m), 6.48 (1H, d, J=9.39 Hz), 7.21 (1H, d, J=9.39 Hz) ppm; LC/MS m/z: 265 (M+1).

Provenance & Evidence