Phosphorus oxychloride → Ethyl 6-bromo-4-chloroquinoline-3-carboxylate

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Reaction Steps

2-[(4-Bromophenylamino)methylene]malonic acid diethyl ester (5 g) was heated with POCl3 (phosphoryl chloride, 31.5 mL) at 150° C. in a sealed tube for about 6 h. The excess POCl3 was removed by rotavapor and the crude mixture was diluted with dichloromethane. The dichloromethane extract was washed with 10% NaOH solution, dried over sodium sulphate and purified by column chromatography (Silica gel, hexane/ethyl acetate 80:20) to give 2.3 g (50%) of 6-bromo-4-chloroquinoline-3-carboxylic acid ethyl ester. 1H NMR (300 MHz, CDCl3) δ 9.22 (s, 1H, aromatic), 8.60 (d, 1H, J=2.1 Hz, aromatic), 8.04 (d, 1H, J=9 Hz, aromatic), 7.95-7.85 (m, 1H, aromatic), 4.53 (q, 2H, J=7 Hz, —CH2—), 1.50 (t, 3H, J=7 Hz, —CH3); LC-MS (m/z) 315.8 (M+1).

Provenance & Evidence