Hydrochloric Acid → 1-Benzyl-5-hydroxy-2-oxo-3-(4-trifluoromethyl-phenyl)-1,2-dihydro-[1,7]naphthyridine-6-carboxylic acid methyl ester

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Reaction Conditions

Reaction Steps

A mixture of 1-benzyl-3-bromo-5-hydroxy-2-oxo-1,2-dihydro-[1,7]naphthyridine-6-carboxylic acid methyl ester (220 mg, 0.57 mmol), 4-(trifluoromethyl)phenylboronic acid (161 mg, 0.85 mmol), K3PO4 (240 mg, 1.13 mmol), H2O (20 mg, 1.13 mmol), SPhos (12 mg, 0.028 mmol) and Pd(OAc)2 (12 mg, 0.017 mmol) in toluene (10 mL) was heated at 105° C. under nitrogen atmosphere for 20 h. After the mixture was cooled to r.t., water and EtOAc were added. 1 M HCl was added until pH was about 3, and the aqueous layer was extracted with additional EtOAc. The organic layers were combined, dried over MgSO4 and concentrated. The crude product was purified by silica gel chromatography (5-50% EtOAc/hexanes+1% AcOH) to give 169 mg of the title compound as a yellow solid. MS: (+) m/z 455.34 (M+1).

Provenance & Evidence