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

Temperature

-78 °C

To a solution of diisoproplyamine (5.3 g, 53 mmol) in anhydrous THF (40 mL) at −30° C. was added n-BuLi (23.2 mL, 58 mmol, 2.5M in hexanes) dropwise. The mixture was stirred at the same temperature for 0.5 h, then cooled to −78° C. and HMPA (0.86 g, 4.8 mmol) was added slowly. Then the solution of 4-bromothiophene-3-carboxylic acid (5.0 g, 24 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 (8.0 g, 48 mmol) was added dropwise 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 was washed with DCM (10*50 mL). The title compound was dissolved in DCM; the solid insoluble in DCM was the side product. 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 compound (0.8 g, yield 10.7%) as a yellow 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 was washed with DCM (10*50 mL)
6. dissolutionThe title compound was dissolved in DCM
7. extractionThe filtrate was extracted with DCM (3×200 mL)
8. dry with materialThe organic layers were dried over Na2SO4
9. concentrationconcentrated under reduced pressure
10. washThe crude product was washed with DCM

ORD record

ord-e29059c55ea0422fabd601d319bdd61e

Source dataset

uspto-grants-2016_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09273068B2