反应详情

To a solution of ethyl 2,4-dimethylpyridine-3-carboxylate (0.59 g, 3.29 mmol) and cyclopropane carboxylic acid (1.2 ml (15.1 mmol) in 10% aqueous H2SO4 (3 ml) was added AgNO3 (154 mg, 0.91 mmol) followed by a solution of ammonium persulfate (1:541 g, 6.75 mmol) in water (6 ml) and the mixture stirred at room temperature overnight. The reaction was neutralized to pH 10 with saturated aqueous NH4OH (5 ml) and extracted with EtOAc (3×20 ml). The combined organic extracts were dried (Na2SO4), concentrated and purified by column chromatography on silica gel (Hexanes/EtOAc, 96:4 then 1:1 then 0:100) to afford desired 6-cyclopropyl-2,4-dimethyl-nicotinic acid ethyl ester (133 mg, 18%) as a clear oil along with recovered starting ethyl 2,4-dimethylpyridine-3-carboxylate (0.31 g). 1H NMR (CDCl3) δ 0.93-0.97 (m, 4H), 1.38 (t, 3H, J=6 Hz), 1.92-2.02 (m, 1H), 2.28 (s, 3H), 2.47 (s, 3H), 4.39 (q, 2H, J=6 Hz), 6.73 (s, 1H).

1. extractionextracted with EtOAc (3×20 ml)
2. dry with materialThe combined organic extracts were dried (Na2SO4)
3. concentrationconcentrated
4. custompurified by column chromatography on silica gel (Hexanes/EtOAc, 96:4