Methyl iodide → 4-Chloro-2-ethylpyridine

Temperature

-20 °C

To a stirred solution of diisopropylamine (0.86 ml, 6.1 mmol) in THF (15 ml) at −20° C. was added dropwise a solution of n-butyllithium in hexanes (1.2M, 5.07 ml, 6.1 mmol). The reaction mixture was stirred at −20° C. for 20 minutes and was then cooled to −70° C. A solution of 2-methyl-4-chloropyridine (0.74 g, 5.8 mmol) in THF (10 ml) was added dropwise over 20 minutes and the reaction mixture was stirred for 1 hour at −70° C. Methyl iodide (0.38 ml, 6.1 mmol) was then added dropwise and the reaction was allowed to warm to room temperature with stirring. The solvent was evaporated at reduced pressure and the resulting residue purified by FCC. 1H NMR indicated a ˜2.2:1 mixture of 2-ethyl and 2-(1-methylethyl) compounds. Re-purification by silica FCC [pentane/ether eluting with gradient 9:1 to 1:1] gave the title compound (209 mg, 24%) as colourless oil.

1. temperaturewas then cooled to −70° C
2. stirringthe reaction mixture was stirred for 1 hour at −70° C
3. temperatureto warm to room temperature
4. stirringwith stirring
5. customThe solvent was evaporated at reduced pressure
6. customthe resulting residue purified by FCC
7. additiona ˜2.2:1 mixture of 2-ethyl and 2-(1-methylethyl) compounds

ORD record

ord-10956a8ae49a4c36bf5037a52a2e12e1

Source dataset

uspto-grants-2014_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08691804B2