Phosphorus oxychloride → 4-Chloro-7-methoxy-2-phenylquinoline

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Reaction Steps

The product of Step 1a (21.7 g, 86.4 mmole) was suspended in POCl3 (240 mL). The suspension was refluxed for 2 hours. After removal of the POCl3 in vacuo, the residue was partitioned between EtOAc (IL), and cold aqueous NaOH (generated from 1.0N 200 mL NaOH and 20 mL 10.0 N NaOH) and stirred for 15 min. The organic layer was washed with water (2×200 mL), brine (200 mL), dried (MgSO4), and concentrated in vacuo to supply 4-chloro-2-phenyl-7-methoxyquinoline (21.0 g, 90%) as a light brown solid. 1H NMR (DMSO-d6) δ: 3.97 (s, 3H), 7.36 (dd, J=9.2, 2.6 Hz, 1H), 7.49-7.59 (m, 4H), 8.08 (d, J=9.2 Hz, 1H), 8.19 (s, 1H), 8.26-8.30 (m, 2H); 13C NMR (DMSO-d6) δ: 55.72, 108.00, 116.51, 119.52, 120.48, 124.74, 127.26, 128.81, 130.00, 137.58, 141.98, 150.20, 156.65, 161.30. LC-MS (retention time: 1.547, Method D), MS m/z 270 (M++1).

Provenance & Evidence