tert-Butyl acrylate → (E)-3-[4-(4-Methoxy-benzyl)-2-oxo-2,3,4,5-tetrahydro-1H-pyrido[2,3-e][1,4]diazepin-7-yl]acrylic acid tert-butyl ester

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Reaction Steps

tert-Butyl acrylate (972 μL, 6.64 mmol), diisopropylethylamine (612 μL, 3.47 mmol) and P(o-tolyl)3 (100 mg, 0.33 mmol) were successively added to a suspension of 7-bromo-4-(4-methoxybenzyl)-4,5-dihydro-1H-pyrido[2,3-e][1,4]diazepin-2(3H)-one (600 mg, 1.66 mmol) in propionitrile (10 mL) and dimethylformamide (2 mL). The resulting mixture was then purged with argon prior to the addition of palladium acetate (40 mg, 0.16 mmol). The mixture was purged with argon a second time 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 (30 mL). The aqueous phase was separated and extracted with ethyl acetate (2×40 mL). The combined organic phases were washed with a saturated solution of sodium chloride (2×20 mL), dried over sodium sulfate, filtered and concentrated to dryness. The residue was purified by chromatography on silica gel, using dichloromethane/ethyl acetate (7:3) as eluent. The title product was obtained as a yellow solid (112 mg, 16%).

Provenance & Evidence