Dimethylformamide → 3-Tert-butoxy-5-chloropyrazine-2-carboxaldehyde

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 5 minutes, the mixture was cooled on ice and stirred for an additional 20 minutes. It was then cooled to −78° C., and a solution of 9.00 g of 2-tert-butoxy-6-chloropyrazine in tetrahydrofuran (10 ml) was added dropwise at below −70° C. The mixture was then stirred for 30 minutes, and 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 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 after 5 minutes, 100 ml of water was added and the temperature was raised to room temperature. The reaction solution was extracted with ethyl acetate, washed with water, a 1N sodium hydroxide solution, water and saturated brine in that order, and dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure to obtain 9.39 g of crude 3-tert-butoxy-5-chloropyrazine-2-carboxaldehyde.

1. temperaturethe mixture was cooled on ice
2. stirringstirred for an additional 20 minutes
3. temperatureIt was then cooled to −78° C.
4. stirringThe mixture was then 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. washwashed with water
12. dry with materiala 1N sodium hydroxide solution, water and saturated brine in that order, and dried over anhydrous magnesium sulfate
13. distillationThe solvent was distilled off under reduced pressure

ORD record

ord-c50da62b6e13438eb64bf75f827d933b

Source dataset

uspto-grants-2011_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07915274B2