Methyl iodide → 3,5-Dibromo-4-methylpyridine

Temperature

-78 °C

Under argon, an n-butyllithium solution in hexane (1.6N, 16 ml) is added dropwise to a diisopropylamine solution (3.6 ml, 1.02 equiv.) in anhydrous THF (145 ml) kept at −10° C. The reaction mixture is cooled to −78° C. and then a 3,5-dibromopyridine solution (5.92 g, 25 mmol) in THF (200 ml) cooled to −78° C. is added dropwise. The reaction mixture is stirred for 30 min and then methyl iodide (2.17 ml, 1.4 equiv.) is added dropwise. The stirring is maintained for 2 h at −78° C. A saturated aqueous NH4Cl solution (120 ml) is added. After evaporation of the solvents, the reaction mixture is extracted with AcOEt. The organic phase is washed with brine, dried over MgSO4 and evaporated. The yellow solid obtained is taken up in AcOEt. The suspension is filtered. The filtrate is evaporated and then the residue is chromatographed on silica gel, eluting with a petroleum ether/AcOEt (97.5/2.5) mixture.

1. customkept at −10° C
2. additionis added dropwise
3. temperatureThe stirring is maintained for 2 h at −78° C
4. customAfter evaporation of the solvents
5. extractionthe reaction mixture is extracted with AcOEt
6. washThe organic phase is washed with brine
7. dry with materialdried over MgSO4
8. customevaporated
9. customThe yellow solid obtained
10. filtrationThe suspension is filtered
11. customThe filtrate is evaporated
12. customthe residue is chromatographed on silica gel
13. washeluting with a petroleum ether/AcOEt (97.5/2.5) mixture

ORD record

ord-c82b9a8b9d374b8caa493b0744b8dcc6

Source dataset

uspto-grants-2009_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07482342B2