Hydrochloric Acid → 3,5-Dichloro-2-methylpyrazine

Temperature

0 °C

To a solution of n-butyllithium (3.8 mL, 2.5M in hexane, 9.4 mmol) in THF (40 mL) cooled to −30° C. under nitrogen was added 2,2,6,6-tetramethylpiperidine (1.7 mL, 10.1 mmol). This solution was allowed to warm to 0° C. over 20 min. and was then cooled to −70° C. A solution of 2,6-dichloropyrazine (1 g, 6.7 mmol) in THF (40 mL) was added dropwise and the resulting brown solution stirred at −70° C. for 30 min. Iodomethane (4.1 mL, 67 mmol) was then added and the solution stirred at −70° C. for a further 45 min after which time a mixture of ethanol (5 mL), THF (5 mL) and 1N HCl (1 mL) was added. The solution was allowed to warm to room temperature and was concentrated under reduced pressure. The residue was dissolved in H2O (50 mL) and the product extracted into dichloromethane (3×30 mL). The combined organic layers were washed with H2O (50 mL) and brine (50 mL) and dried (Na2SO4). The organic layer was concentrated in vacuo and the residue purified by column chromatography eluting with dichloromethane-hexane (1:1) to separate the product as a clear motile oil (820 mg).

1. temperaturewas then cooled to −70° C
2. stirringthe solution stirred at −70° C. for a further 45 min after which time
3. additionwas added
4. temperatureto warm to room temperature
5. concentrationwas concentrated under reduced pressure
6. dissolutionThe residue was dissolved in H2O (50 mL)
7. extractionthe product extracted into dichloromethane (3×30 mL)
8. washThe combined organic layers were washed with H2O (50 mL) and brine (50 mL)
9. dry with materialdried (Na2SO4)
10. concentrationThe organic layer was concentrated in vacuo
11. customthe residue purified by column chromatography
12. washeluting with dichloromethane-hexane (1:1)
13. customto separate the product as a clear motile oil (820 mg)

ORD record

ord-1feb83b6085e4ee38d4789d77bff097f

Source dataset

uspto-grants-2011_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08084456B2