Phosphorus oxide (P4O10) → 1-(3-Fluoro-4-(trifluoromethyl)phenyl)-3,4-dihydroisoquinoline

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Reaction Steps

To a stirred mixture of 3-fluoro-N-phenethyl-4-(trifluoromethyl)benzamide (1.27 g, 4.08 mmol) in 30 mL of toluene, phosphorus pentoxide (1.751 g, 12.3 mmol) and phosphorus oxychloride (1.90 mL, 20.4 mmol) were added. The mixture was refluxed for overnight. The reaction mixture was cooled to RT. Supernatant was removed and the ice-water was added to the flask containing the residue. The mixture was stirred to break the chunks into powder. EtOAc was added and the pH was adjusted to ˜12 with 3N aqueous potassium hydroxide. The layers were separated and the aqueous phase was extracted with EtOAc. The combined organic phases were washed with water and saturated aqueous sodium chloride. The organic phase was dried over sodium sulfate, filtered and concentrated in vacuo to afford 0.887 g of yellow viscous oil. The crude product was purified by silica gel chromatography (0-30% EtOAc in hexanes) to afford the title compound as a clear oil. 1H NMR (300 MHz, CHLOROFORM-d) δ ppm 7.63-7.73 (m, 1H) 7.39-7.54 (m, 3H) 7.31 (d, J=7.60 Hz, 2H) 7.16-7.24 (m, 1H) 3.84-3.96 (m, 2H) 2.77-2.89 (m, 2H).

Provenance & Evidence