p-Nitroacetophenone → 1-(2-Methoxy pyridine-3-yl)-3-(4-nitrophenyl)propane-1,3-dione

Participants

Reaction Conditions

Reaction Steps

To a stirred solution of 2-methoxynicotinic acid (2.3 g, 15 mmol) in 75 mL anhydrous THF was added N-methyl morpholine (1.52 g, 15 mmol). The reaction mixture was cooled to −10° C. Ethylchloroformate (1.63 g, 15 mmol) was added dropwise at −10° C. The reaction mixture was stirred at −10° C. for 15 min. and then at rt for 10 h. Water (50 mL) was added, and the solution was extracted with ethyl acetate. The organic layer was separated, dried (Na2SO4), and concentrated to give a colorless liquid in 97% yield (3.29 g). To a solution of this colorless liquid (3.28 g, 14.57 mmol) and 4′-nitroacetophenone (2.477 g, 15 mmol) in anhydrous THF (75 mL) was added lithium bis(trimethylsilyl)amide 1.0M solution in THF (18 mL) at −30° C. over a period of 45 min. Stirring continued at −30° C. for 30 min. The reaction mixture was allowed to warm to rt. The stirring was continued for another 15 h at rt, and the reaction mixture was then diluted with ethyl acetate (200 mL). Saturated NH4Cl solution (50 mL) was added. The organic layer was separated and dried over anhydrous Na2SO4. Removal of solvent gave the crude product which was triturated with ether to give 1-(2-methoxy pyridine-3-yl)-3-(4-nitrophenyl)propane-1,3-dione as yellow solid in 62% yield (2.79 g).

Provenance & Evidence