Diethyl Ether → 2-Acetyl-6-bromopyridine

Temperature

20 °C

2,6-dibromopyridine (10.0 g, 42.2 mmol) was placed in a reaction flask. To ensure a nitrogen atmosphere in the reaction flask, the gas in the reaction flask was drawn out and the reaction flask was refilled with nitrogen gas in a rapid manner three times. To the reaction flask, 150 ml of anhydrous diethylether was added, and then 17.7 ml of an n-butyllithium solution (44.3 mmol, 2.5 M in n-hexane) was slowly added at −78° C. to obtain a mixture. In the meanwhile, the color of the mixture changed from transparent to yellowish-brown. The mixture in the reaction flask was kept at −78° C. and continuously stirred for 30 minutes. Then, N,N-dimethylacetamide (4.7 ml, 50.7 mmol) was slowly added to the mixture, and the mixture was kept at −78° C. for 3 hours for reaction. Thereafter, the temperature of the mixture was slowly raised to 20° C. At this moment, the color of the mixture in the reaction flask changed to cloudy gray. Deionized water was slowly added to the mixture to terminate the reaction in the reaction flask. The solvents in the mixture were drawn out of the reaction flask, and the residue in the reaction flask was washed several times with ethyl acetate and with a saturated sodium chloride solution to collect an organic layer, followed by dehydration of the organic layer using sodium sulfate (Na2SO4) to thereby obtain a crude product. The crude product was subjected to column chromatography (SiO2, ethyl acetate:n-hexane=1:20), followed by recrystallization in a mixed solvent having dichloromethane and n-hexane (dichloromethane:n-hexane=1:20) at 20° C., thereby obtaining white crystals (6.80 g, 81% yield).

1. additionthe reaction flask was refilled with nitrogen gas in a rapid manner three times
2. customto obtain a mixture
3. customwas kept at −78° C.
4. customthe mixture was kept at −78° C. for 3 hours for reaction
5. customto terminate
6. customthe reaction in the reaction flask
7. washthe residue in the reaction flask was washed several times with ethyl acetate
8. customwith a saturated sodium chloride solution to collect an organic layer
9. customto thereby obtain a crude product
10. customfollowed by recrystallization in a mixed solvent
11. customat 20° C.

ORD record

ord-c34a63d4d61b471caeb892956028e4ee

Source dataset

uspto-grants-2015_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09219237B1