Methyl iodide → 1-methyl-4-trifluoromethyl-1H-quinolin-2-one

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Reaction Steps

KOH (10.54 g, 188.0 mmol) was added to a solution of 4-trifluoromethyl-1H-quinolin-2-one (4.00 g, 18.8 mmol) in DMF (160 mL). After 1 hour, the mixture was treated with MeI (11.7 mL, 188.0 mmol), then stirring was continued overnight. EtOAc (200 mL) was added, followed by saturated aqueous NH4Cl to adjust the aqueous pH to 6.5. After separation of the layers, the aqueous phase was extracted further with EtOAc (2×200 mL). The combined organic extracts were washed with H2O (200 mL) and brine (200 mL), before being dried (MgSO4). Filtration, solvent evaporation, and column chromatography (PE-EtOAc, 4:1 to 7:3) yielded 1-methyl-4-trifluoromethyl-1H-quinolin-2-one (4.00 g, 94%): δH ((CD3)2SO)=3.65 (s, 3H), 7.10 (s, 1H), 7.40 (t, 1H), 7.65–7.80 (m, 3H). This compound (8.70 g, 38.3 mmol) was added portionwise with stirring over 20 min to fuming H2SO4 (30% oleum, 17.5 mL) at 84° C. The bath temperature was raised to 120° C. for 1 hour, before being cooled back down to 20° C. Thereupon, the mixture was added slowly to saturated aqueous NaCl (60 mL) and stirred for 30 min. The solid produced was collected & dried under vacuum at 50° C. to give sodium 1-methyl-2-oxo-4-trifluoromethyl-1,2-dihydroquinoline-6-sulfonate: δH((CD3)2SO)=3.65 (s, 3H), 7.10 (s, 1H), 7.65 (d, 1H), 7.95 (dd, 1H), 8.00 (d, 1H). This compound was suspended in MeCN-sulfolane (1:1, 52 mL), before being treated with POCl3 (18.8 mL, 201.7 mmol). The mixture was heated to 88° C. for 1.5 hours, before being cooled to 20° C. over 0.5 hour. On cooling to <5° C., ice cold H2O (128 mL) was added, the temperature being maintained below 7° C. The mixture was stirred at 0° C. for 20 minutes, then the solid formed was collected and washed with H2O to afford, after drying, the title compound (9.62 g, 73%): δH (CDCl3)=3.80 (s, 3H), 7.25 (s, 1H), 7.65 (d, 1H), 8.25 (dd, 1H), 8.50 (d, 1H). Preparation 2: 2-Oxo-4-trifluoromethyl-2H-chromene-6-sulfonyl chloride

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