Hexachloroethane → N-(3,6-dichloropyridin-2-yl)pivalamide

Temperature

0 °C

To a solution of N-(6-chloropyridin-2-yl)pivalamide (2.00 g, 9.40 mmol) in 25 mL THF at −78° C. was added butyllithium 2.5 M in hexanes (9.40 mL, 23.5 mmol) slowly dropwise over 2 min After 5 min, the reaction mixture was warmed to 0° C., then back to −10° C. (ice/brine) and to −20° C. (ice/salt). The reaction mixture was allowed to stir at this temp for 1.5 h. The reaction mixture was cooled to −78° C. and a solution of hexachloroethane (3.34 g, 14.1 mmol) in 7.5 mL THF was added dropwise via syringe. The bath was removed and the reaction mixture warmed to ambient temperature. The reaction mixture was partitioned between satd NH4Cl and Et2O. The organic layer was washed with water once, brine once, and the organics were dried over anhydrous sodium sulfate, filtered, and concentrated in vacuo. The material was dissolved in DCM and purified by silica gel chromatography, 80 g, 5-50% EA/hexanes. Product-containing fractions were combined and concentrated to give N-(3,6-dichloropyridin-2-yl)pivalamide as a solid. MS (ESI) m/z: calculated: 246.0; Observed: 247.0 (M++1).

1. customback to −10° C.
2. customto −20° C.
3. temperatureThe reaction mixture was cooled to −78° C.
4. customThe bath was removed
5. temperaturethe reaction mixture warmed to ambient temperature
6. customThe reaction mixture was partitioned between satd NH4Cl and Et2O
7. washThe organic layer was washed with water once
8. dry with materialbrine once, and the organics were dried over anhydrous sodium sulfate
9. filtrationfiltered
10. concentrationconcentrated in vacuo
11. dissolutionThe material was dissolved in DCM
12. custompurified by silica gel chromatography, 80 g, 5-50% EA/hexanes
13. concentrationconcentrated

ORD record

ord-ff7b98e8dd664fefa3a868cc9ea56d32

Source dataset

uspto-grants-2010_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07842685B2