Sodium hydride → 6-((2,2,2-Trifluoroethoxy)methyl)nicotinic acid

참여 물질

반응 단계

To a solution of methyl 6-(hydroxymethyl)nicotinate (500 mg, 2.99 mmol) in tetrahydrofuran (30 mL) was added sodium hydride 60% dispersion in mineral oil (126 mg, 3.14 mmol) and the reaction mixture was stirred at ambient temperature for 5 min. 2,2,2-trifluoroethyl trifluoromethanesulphonate (729 mg, 3.14 mmol) was added and the reaction mixture was stirred at ambient temperature for 4 h. Additional sodium hydride (42 mg, 1.05 mmol) was added followed by 2,2,2-Trifluoroethyl trifluoromethanesulphonate (243 mg, 1.45 mmol) after 5 min. Water (20 mL) was added carefully followed by lithium hydroxide monohydrate (0.376 g, 8.97 mmol) and the formed reaction mixture was stirred at ambient temperature for 5.5 h. The solvent was partially removed in vacuo and 1M hydrochloric acid added until an acidic pH was reached. The mixture was extracted with ethyl acetate (3×25 mL) and the combined organic layer was dried over magnesium sulfate and concentrated in vacuo. Purification by column chromatography using a gradient of methanol in dichloromethane yielded 171 mg (24%) of the title compound; 1H NMR (400 MHz, DMSO-d6) δ ppm 9.02 (dd, 1 H), 8.32 (dd, 1 H), 7.56 (dd, 1 H), 4.84 (s, 2 H), 4.26 (q, 2 H); MS (ESI) m/z 236[M+H+].

출처 및 근거