Thiophene-3-carboxylic acid → 2-Isonicotinoylthiophene-3-carboxylic acid

Participants

Reaction Conditions

Reaction Steps

To a solution of diisopropylamine (5.2 g, 51.5 mmol) in anhydrous THF (40 mL) at −30° C. was added n-BuLi (23.2 mL, 56.2 mmol, 2.5M in THF) dropwise. The mixture was stirred at the same temperature for 0.5 h, then cooled to −78° C. and HMPA (0.8 g, 4.7 mmol) was added slowly. Then a solution of thiophene-3-carboxylic acid (3.0 g, 23.4 mmol) in anhydrous THF (50 mL) was added slowly. The mixture was stirred at the same temperature for 1 h, N-methoxy-N-methyl-4-pyridinecarboxamide (5.0 g, 46.9 mmol) was added drop wise into the stirring mixture at −78° C. The reaction mixture was stirred for another 1 h at room temperature and was then quenched with H2O (10 mL). The aqueous layer was acidified with 5% aq. HCl to pH 1-2, the precipitate was collected by filtration. The filter cake wash with DCM and the filtrate was extracted with DCM (3×200 mL). The organic layers were dried over Na2SO4 and concentrated under reduced pressure. The crude product was washed with DCM to give the title product (2.2 g, yield 40%) as a white solid.

Provenance & Evidence