Dimethylformamide → 5-Chloro-3-methoxypyrazine-2-carbaldehyde

Temperature

-30 °C

After dissolving 11.4 ml of 2,2,6,6-tetramethylpiperidine in 100 ml of tetrahydrofuran, the solution was cooled to −30° C. Next, 24.1 ml of n-butyllithium (2.6 M, n-hexane solution) was added dropwise under a nitrogen atmosphere. After stirring for 15 minutes and cooling on ice, the mixture was stirred for 10 minutes. It was then cooled to −78° C., and a solution of 6.96 g of 2-chloro-6-methoxypyrazine in tetrahydrofuran (10 ml) was added dropwise at below −70° C. The mixture was stirred for 30 minutes, and then 6 ml of N,N-dimethylformamide was added dropwise at below −65° C. After 10 minutes, 50 ml of toluene was added to the reaction solution at below −60° C., and then after 2 minutes, a tetrahydrofuran solution (5 ml) containing 2 ml of water was added at below −65° C. After an additional 5 minutes, 60 ml of 50% aqueous acetic acid was added at once, and then after 15 minutes, 100 ml of water was added and the temperature was raised to room temperature. The reaction solution was extracted with ethyl acetate, and the organic layer was washed with water, a 1N sodium hydroxide solution and saturated brine in that order and dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure and the residue was purified by silica gel column chromatography (solvent: n-hexane/ethyl acetate) to obtain the title compound (6.38 g, 77% yield).

1. temperaturecooling on ice
2. stirringthe mixture was stirred for 10 minutes
3. temperatureIt was then cooled to −78° C.
4. stirringThe mixture was stirred for 30 minutes
5. waitAfter 10 minutes
6. waitafter 2 minutes
7. additionwas added at below −65° C
8. waitAfter an additional 5 minutes
9. temperaturethe temperature was raised to room temperature
10. extractionThe reaction solution was extracted with ethyl acetate
11. washthe organic layer was washed with water
12. dry with materiala 1N sodium hydroxide solution and saturated brine in that order and dried over anhydrous magnesium sulfate
13. distillationThe solvent was distilled off under reduced pressure
14. customthe residue was purified by silica gel column chromatography (solvent: n-hexane/ethyl acetate)

ORD record

ord-af5eca0f804c42a8a491bb75c21f9693

Source dataset

uspto-grants-2011_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07915274B2