Acetic Acid → 3,4-Dichloropyridine-2-carboxamide

Temperature

0 °C

To a mixture of 2,2,6,6-tetramethylpiperidine (6.2 mL, 37.2 mmol) in diethylether (50 mL) was added n-BuLi in hexane (2.5M, 23 mL, 57.5 mmol) at 0° C. via syringe over 15 min. The mixture was stirred at 0° C. for 0.5 hour, then cooled to −78° C. A solution of 3,4-dichloropyridine (5.00 g, 33.8 mmol) in diethylether (20 mL) was added to the mixture via a syringe over 15 minutes. The reaction was stirred at −78° C. for 2 hours, then isocyanatotrimethylsilane (94% pure, 6.7 mL, 50.7 mmol) was added. The mixture was warmed up to rt and further stirred for 2 hours, quenched with acetic acid (6.76 g, 112.6 mmol) in 35 mL of water. The mixture was further stirred overnight. The titled product was precipitated overnight as a white solid, which was collected through filtration. More products were recovered from the filtrate. Thus, the filtrate was extracted with ethyl acetate (50 mL×3) and the combined organic phases were washed with brine (50 mL), dried over anhydrous Na2SO4, and concentrated in vacuo. The solid was combined and washed with 35 mL of Et2O to give the title compound as a pale yellow solid (2.20 g, 34.0%).

1. temperaturecooled to −78° C
2. stirringThe reaction was stirred at −78° C. for 2 hours
3. temperatureThe mixture was warmed up to rt
4. stirringfurther stirred for 2 hours
5. stirringThe mixture was further stirred overnight
6. customThe titled product was precipitated overnight as a white solid, which
7. filtrationwas collected through filtration
8. customMore products were recovered from the filtrate
9. extractionThus, the filtrate was extracted with ethyl acetate (50 mL×3)
10. washthe combined organic phases were washed with brine (50 mL)
11. dry with materialdried over anhydrous Na2SO4
12. concentrationconcentrated in vacuo
13. washwashed with 35 mL of Et2O

ORD record

ord-bddd1ede9e4540449f2b9cbd095d5991

Source dataset

uspto-grants-2016_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09326975B2