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

Temperature

-60 °C

2-Acetyl-6-bromopyridine was synthesized by the method of J. E. Parks, B. E. Wagner, and R. E. Holm, J. Organometal. Chem 56, 53-66 (1973) from 2,6-bromopyridine, 1. 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) in hexane 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 H2 O 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 subjected to Kugelrohr distillation at 80° C./0.1 mm Hg to give 257 g (86%) of a product as a nearly colorless oil that crystallized readily on cooling. The compound exhibited a single spot in a silica gel thin layer chromatography (TLC) analytical system using 90% hexane: 10% ether (vol/vol).

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 H2 O and once with saturated salt solution
15. dry with materialThe organic layer was dried over MgSO4
16. customafter evaporating to dryness

ORD record

ord-02154a4c03d34449a726e8898edb9748

Source dataset

uspto-grants-1998_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05760191