Sodium Hydroxide → 2-(Trifluoromethyl)-5,6,7,8-tetrahydroquinoline-6-carboxylic acid

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Reaction Steps

A mixture of ethyl 2-(trifluoromethyl)-5,6,7,8-tetrahydroquinoline-6-carboxylate (0.47 g, 1.7 mmol), 1 M aqueous sodium hydroxide (3.4 mL, 3.4 mmol, 2 equiv.) and methanol (10 mL), was heated at reflux for 16 h. The mixture was concentrated to remove MeOH, diluted with 1M aqueous NaH2PO4 (15 mL) and buffered to pH 3 with 1M H3PO4, depositing a voluminous precipitate. The mixture was extracted with DCM (3×30 mL), and the combined organic layers were dried (Na2SO4), filtered and concentrated. The solid residue was purified by reverse-phase HPLC (40-55% acetonitrile in 0.1% HCO2H/H2O). The combined HPLC fractions were concentrated to remove acetonitrile, buffered with 1M NaH2PO4 (10 mL) and extracted with DCM (3×30 mL). The combined organic layers were dried (Na2SO4), filtered and concentrated to afford the acid as a solid (324 mg, 77%). 1H NMR (400 MHz, DMSO-d6) [δ] 12.45 (s, 1H), 7.82 (d, J=7.9 Hz, 1H), 7.63 (d, J=7.9 Hz, 1H), 3.12-2.86 (m, 4H), 2.83-2.76 (m, 1H), 2.22-2.14 (m, 1H), 1.97-1.86 (m, 1H); m/z=246.1 (M+H)+.

Provenance & Evidence