Diisopropylamine → 4-Bromo-2-isonicotinoylthiophene-3-carboxylic acid

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Reaction Steps

To a solution of (i-Pr)2NH (5.3 g, 53 mmol) in anhydrous THF (40 mL) at −78° C. was added n-BuLi (23.2 mL, 58 mmol, 2.5M in hexane) dropwise. The mixture was stirred at the same temperature for 0.5 h. Then a solution of 4-Bromothiophene-3-carboxylic acid (5.0 g, 24 mmol) and HMPA (0.86 g, 4.8 mmol) in anhydrous THF (50 mL) was slowly added. The mixture was stirred at the same temperature for 1 h and N-methoxy-N-methyl-4-pyridine carboxamide (8.0 g, 48 mmol) was added dropwise to the stirring mixture at −78° C. The reaction mixture was stirred for another hour at room temperature and was then quenched with H2O. The aqueous layer was acidified with 5% aq. HCl to pH 1˜2. The precipitate was removed by filtration and the resulting filtrate extraxted with CH2Cl2 (3×200 mL). The organic layers were dried over Na2SO4 and concentrated under reduced pressure. The crude product was washed with CH2Cl2 to give the title compound (1.6 g, 20% yield) as a yellow solid. LC-MS (Method A): m/z 312 (M+H)+, Rt: 0.55 min. 1H NMR (400 MHz, DMSO-d6): δ=13.61 (s, 1H), 8.81-8.80 (m, 2H), 8.25 (s, 1H), 7.67-7.65 (m, 2H).

Provenance & Evidence