Methyl iodide → 3,5-Dichloro-2-methylpyrazine

Temperature

0 °C

To a solution of n-butyl lithium (1.6M in hexanes; 29 mL, 47 mmol) in tetrahydrofuran (200 mL) at −30° C. was added 2,2,6,6-tetramethylpiperidine (8.6 mL, 50 mmol). This solution was allowed to warm to 0° C. over 20 minutes then cooled to −78° C. To this solution was added a solution of 2,6-dichloropyrazine (5 g, 34 mmol) in tetrahydrofuran (200 mL) dropwise via cannula. After 30 minutes, iodomethane (21 mL, 340 mmol.) was added. After 1 h, the reaction mixture was quenched with a mixture of EtOH (25 mL), THF (25 mL) and 1N aqueous HCl (5 mL). The reaction mixture was allowed to warm to room temperature then concentrated to a crude oil. The crude oil was partitioned between water (500 mL) and CH2Cl2 (500 mL). The organic layer was washed with brine (250 mL). The first aqueous layer was back-extracted with CH2Cl2 (500 mL). The combined organic layers were dried over sodium sulfate, filtered and concentrated. The crude residue was purified by silica gel chromatography (EtOAc/Hexanes gradient) to afford 3,5-dichloro-2-methylpyrazine as a yellow oil. LRMS (ESI) calculated for C5H4Cl2N2 [M+H]+, 163.0; found 163.1.

1. temperaturethen cooled to −78° C
2. waitAfter 1 h
3. customthe reaction mixture was quenched with a mixture of EtOH (25 mL), THF (25 mL) and 1N aqueous HCl (5 mL)
4. temperatureto warm to room temperature
5. concentrationthen concentrated to a crude oil
6. customThe crude oil was partitioned between water (500 mL) and CH2Cl2 (500 mL)
7. washThe organic layer was washed with brine (250 mL)
8. extractionThe first aqueous layer was back-extracted with CH2Cl2 (500 mL)
9. dry with materialThe combined organic layers were dried over sodium sulfate
10. filtrationfiltered
11. concentrationconcentrated
12. customThe crude residue was purified by silica gel chromatography (EtOAc/Hexanes gradient)

ORD record

ord-8a325c5622f54a2785b3fc49f5ab648f

Source dataset

uspto-grants-2012_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08183245B2