Diisopropylethylamine → (E)-N-{(S)-2-[4-(4-Fluoro-benzoyl)-piperidin-1-yl]-1-hydroxymethyl-ethyl)-3-(5-cyano-2-methoxy-phenyl)-acrylamide

関与物質

反応手順

To a solution of [1-((S)-2-amino-3-hydroxy-propyl)-piperidin-4-yl]-(4-fluoro-phenyl)-methanone hydrochloride (1.8 g, 5.7 mmol) and diisopropylethylamine (2.0 ml, 11.4 mmol) in dichloromethane (45 ml) is added (E)-3-(5-cyano-2-methoxy-phenyl)-acrylic acid (1.1 g, 5.7 mmol) followed by 2-(1H benzotriazol-1-yl)-1,1,3,3,-tetramethyluronium tetrafluoroborate (1.83 g, 5.7 mmol). The reaction mixture is stirred at ambient temperature for 4.5 hours, then filtered and the filtrate washed with water (50 ml), saturated sodium bicarbonate solution (50 ml), water (50 ml) and brine (50 ml). The organic phase is dried over magnesium sulphate, the solvent evaporated and the residue purified by flash silica chromatography (dichloromethane:methanol; 98:2 to 92:8 elution gradient) to afford the product, [MH]+466.1.

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