Hydrochloric Acid → HCID 57249145, compound

Participants

Reaction Conditions

Reaction Steps

4-Methoxy-6-trifluoromethylquinoline (5.0 g, 22.0 mmol) was dissolved in anhydrous tetrahydrofuran (20 mL). The mixture was cooled to -78 ° C., and methyl magnesium chloride (73 mL of a 3.0M solution in tetrahydrofuran, 220 mmol) was added to the resulting slurry. After addition, benzyl chloroformate (41 mL, 286 mmol) was added to the slurry. After stirring at room temperature overnight, 75 mL of methanol was added followed by 75 mL of a 1N aqueous HCl solution. After hydrolysis of the intermediate enol ether was judged to be complete by thin layer chromatography, the volatiles were removed in vacuo, and the remaining aqueous phase was extracted with ethyl acetate (3×150 mL). The organic phases were combined and washed with a saturated sodium bicarbonate solution (2×75 mL), brine (100 mL), dried over sodium sulfate, filtered, and concentrated in vacuo to give 47 g of crude product. Purification by silica gel chromatography using 10% ethyl acetate/hexanes as eluent afforded 5.54 g of the title product (69%).1H NMR (CDCl3) δ 1.25 (d, 3H, J=7 Hz), 2.62 (dd, 1H, J=17, 2 Hz), 3.05 (dd, 1H, J=17, 6 Hz), 5.1-5.2 (m, 1H), 5.28 (d, 1H, J=12 Hz), 5.35 (d, 1H, J=12 Hz), 7.3-7.5 (m, 5H), 7.71 (dd, 1H, J=9,2 Hz), 8.05 (d, 1H, J=9 Hz), 8.27 (d, 1H, J=2 Hz).

Provenance & Evidence