2,6-Dibromopyridine → 2-Acetyl-6-bromopyridine

Temperature

-60 °C

A 5 L 3-neck flask was charged with 2,6-dibromopyridine (181 g; 0.75 mole) and 2.0 L ether. The suspension was stirred under nitrogen at -60° C. and then n-butyllithium (300 mL; 2.5M) was added from a pressure equalizing dropping funnel over 20 minutes. The bath was lowered and the near solution was allowed to warm to -50° C. After 15 minutes, the dark yellow solution was re-cooled to -78° C. in a dry ice/ether bath and dimethylacetamide (70 g; 0.86 mole) in 70 mL ether was added at such a rate that the temperature did not exceed -75° C. The addition took about one hour for completion, after which the bath was removed to allow the reaction to warm to -60° C. A solution of ammonium chloride (50 g; 0.93 mole) in 150 mL of H2O was added dropwise over 10 minutes under nitrogen and the temperature rose to -40° C. The mixture was stirred for 45 minutes and the layers were separated. The aqueous layer was back-extracted with 500 mL ether and the pooled organic layers were washed twice with H20 and once with saturated salt solution. The organic layer was dried over MgSO4 and, after evaporating to dryness, gave 150 g of yellow oil. This material, after pooling with another run of the same scale, was kugelrohred at 80° C./0.1 mm Hg to give 257 g (86%) of a near colorless oil that crystallized readily on cooling; silica gel TLC system: 90 hexane: 10 ether.

1. customover 20 minutes
2. temperatureto warm to -50° C
3. temperaturethe dark yellow solution was re-cooled to -78° C. in a dry ice/ether bath
4. customdid not exceed -75° C
5. additionThe addition
6. waittook about one hour for completion
7. customafter which the bath was removed
8. customthe reaction
9. temperatureto warm to -60° C
10. customrose to -40° C
11. stirringThe mixture was stirred for 45 minutes
12. customthe layers were separated
13. extractionThe aqueous layer was back-extracted with 500 mL ether
14. washthe pooled organic layers were washed twice with H20 and once with saturated salt solution
15. dry with materialThe organic layer was dried over MgSO4
16. customafter evaporating to dryness

ORD record

ord-df31d95c9d894be1aa8b68bf71168868

Source dataset

uspto-grants-1998_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05707603