Diisopropylamine → 4-Bromo-2-(pyridine-4-carbonyl)thiophene-3-carboxylic acid

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).

1. stirringThe mixture was stirred at the same temperature for 1 h
2. stirringThe reaction mixture was stirred for another hour at room temperature
3. customwas then quenched with H2O
4. customThe precipitate was removed by filtration
5. dry with materialThe organic layers were dried over Na2SO4
6. concentrationconcentrated under reduced pressure
7. washThe crude product was washed with CH2Cl2

ORD record

ord-2ee27c940c184f8887d01b24e68e5fe0

Source dataset

uspto-grants-2015_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09200005B2