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

Temperatur

-78 °C

n-BuLi (23.2 mL, 56.2 mmol, 2.5M in THF) was added dropwise to a solution of diisopropylamine (5.2 g, 51.5 mmol) in anhydrous THF (40 mL) at −30° C. The mixture was stirred at the same temperature for 0.5 h and 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. Then N-methoxy-N-methyl-4-pyridinecarboxamide (5.0 g, 46.9 mmol) was added dropwise to 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 and the resulting precipitate collected by filtration. The filter cake was washed 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, 40% yield) as a white solid. LC-MS (Method A): m/z 234 (M+H)+, Rt: 0.57 min.

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 resulting precipitate collected by filtration
5. washThe filter cake was washed 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-47335f10907a48a38929f3cb342daa52

Quelldatensatz

uspto-grants-2015_12

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US09200005B2