Hydrochloric Acid → 3-Acetyl-2-chloropyridine

2-Chloro-N-methoxy-N-methyl-nicotinamide (3.90 g, 19.4 mmol, 1.0 equiv) is dissolved in THF (200 mL) under nitrogen and the mixture is cooled in an ice bath. Methylmagnesium chloride (17.0 ml, 48.6 mmol, 2.5 equiv) is added within 2 minutes. After 15 min a grey precipitate is formed. Stirring is continued for 2 h, the mixture is cooled in an ice bath and sat. NH4Cl (150 mL) is added. The solution is acidified with 1N HCl solution (60 mL) followed by addition of sat. NaHCO3 solution (30 mL). The organic layer is separated and concentrated in vacuo. The residue is combined with the remaining water layer and extracted with diethyl ether (200 mL). The combined etheral layers are washed twice with brine (50 mL), dried over Na2SO4, filtered and concentrated in vacuo. This provides 2.57 g of the title compound as a yellow oil.

1. temperaturethe mixture is cooled in an ice bath
2. customAfter 15 min a grey precipitate is formed
3. temperaturethe mixture is cooled in an ice bath
4. customThe organic layer is separated
5. concentrationconcentrated in vacuo
6. extractionextracted with diethyl ether (200 mL)
7. washThe combined etheral layers are washed twice with brine (50 mL)
8. dry with materialdried over Na2SO4
9. filtrationfiltered
10. concentrationconcentrated in vacuo

ORD record

ord-07d49bd7516a4d5fb4082a0045460895

Source dataset

uspto-grants-2011_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07985753B2