Diisopropylamine → 3,5-Dichloro-2-methylpyridine

N,N-diisopropylamine (65.6 ml) was dissolved in anhydrous THF (150 ml), to which was dropwise added n-butyl lithium (1.54 mols/liter hexane solution, 300 ml) in an argon atmosphere at −78° C., and directly stirred for 5 minutes. An anhydrous THF (600 ml) solution of 3,5-dichloropyridine (63 g) was dropwise added to this, and stirred for 1 hour, and thenmethyl iodide (29.2 ml) was dropwise added thereto, and stirred for further 1.5 hours. Water was added to this to stop the reaction, which was then extracted with ethyl acetate. The organic layer was washed with a saturated saline solution, then dried over magnesium sulfate, and the solvent was distilled under reduced pressure. The residue was purified by silica gel column chromatography (hexane:ethyl acetate=10:1), then suspended in hexane, and taken out through filtration to obtain 3,5-dichloropicoline (62.8 g, 91%) as colorless crystals.

1. customat −78° C.
2. stirringstirred for 1 hour
3. stirringstirred for further 1.5 hours
4. customthe reaction, which
5. extractionwas then extracted with ethyl acetate
6. washThe organic layer was washed with a saturated saline solution
7. dry with materialdried over magnesium sulfate
8. distillationthe solvent was distilled under reduced pressure
9. customThe residue was purified by silica gel column chromatography (hexane:ethyl acetate=10:1)
10. filtrationtaken out through filtration

ORD record

ord-66005af421b34dadbd48e2ff4fca3631

Source dataset

uspto-grants-2003_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06514996B2