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

Temperature

-10 °C

Diisopropylamine (70 mL, 500 mmol) is dissolved in dry tetrahydrofuran (500 mL), the solution is cooled to −10° C. and buthyl lithium (2.5 N in hexane, 210 mL, 525 mmol) is added dropwise under stirring. After 30 minutes the solution is cooled to −20° C. and 3,5-dichloropyridine (66.6 g, 450 mmol) in tetrahydrofuran (200 mL) is added dropwise. The solution is stirred at −10° C. for 30 minutes, then cooled to −70° C. and iodomethane (50 mL, 1.6 mol) in tetrahydrofuran (100 mL) is added dropwise. The reaction mixture is allowed to warm to room temperature, quenched with water (100 mL) and extracted with diethyl ether (3×100 mL); the combined organic layers are dried over sodium sulphate (5 g) and evaporated to dryness. The crude product is crystallized twice from aqueous ethanol, then from hexane to afford 3,5-dichloro-4-methylpyridine (49.9 g, 306 mmol, 68% yield) as a white solid.

1. temperatureAfter 30 minutes the solution is cooled to −20° C.
2. stirringThe solution is stirred at −10° C. for 30 minutes
3. temperaturecooled to −70° C.
4. temperatureto warm to room temperature
5. customquenched with water (100 mL)
6. extractionextracted with diethyl ether (3×100 mL)
7. dry with materialthe combined organic layers are dried over sodium sulphate (5 g)
8. customevaporated to dryness
9. customThe crude product is crystallized twice from aqueous ethanol

ORD record

ord-32836d5f2e024a47b9d4852398f63327

Source dataset

uspto-grants-2011_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07968724B2