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

Temperatur

-78 °C

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.

1. stirringThe mixture was stirred at the same temperature for 1 h
2. stirringThe reaction mixture was stirred for another 1 h at room temperature
3. customwas then quenched with H2O (10 mL)
4. filtrationthe precipitate was collected by filtration
5. washThe filter cake wash with DCM
6. extractionthe filtrate was extracted with DCM (3×200 mL)
7. dry with materialThe organic layers were dried over Na2SO4
8. concentrationconcentrated under reduced pressure
9. washThe crude product was washed with DCM

ORD-Eintrag

ord-0ce64d9263934fa2afafc03ca8eaa3cb

Quelldatensatz

uspto-grants-2016_03

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US09273068B2