tert-Butyl acrylate → tert-butyl (E)-3-(7-oxo-5,6,7,8-tetrahydro-1,8-naphthyridin-3-yl)acrylate

Participants

Reaction Steps

tert-Butyl acrylate (31.2 mL, 210 mmol), diisopropylethylamine (19.4 mL, 110 mmol) and P(o-tolyl)3 (3.2 g, 10.5 mmol) were successively added to a suspension of 6-bromo-3,4-dihydro-1H-1,8-naphthyridin-2-one (11.9 g, 52.5 mmol; which may be prepared as described in D1, Step 5) in propionitrile (83 mL) and dimethylformamide (46 mL). The resulting mixture was then purged with argon prior to the addition of palladium acetate (1.2 g, 5.2 mmol). The mixture was purged with argon again and refluxed overnight. The reaction mixture was then filtered on Celite®. The filtrate was concentrated to dryness and the residue was solubilized in ethyl acetate (200 mL). The resulting solution was washed with a saturated solution of sodium chloride (3×100 mL), dried over sodium sulfate, filtered and concentrated to dryness. The residue was purified by chromatography on silica gel, using dichloromethane/methanol (98:2) as eluent. After trituration with Et2O/petroleum ether (1/1), the title product was obtained as a yellow solid (4.35 g, 40%).

Provenance & Evidence