Dimethylformamide → 3-Chloropyrazine-2-carbaldehyde

Temperature

-78 °C

A flame dried and cooled 100 mL round bottom flask was charged with 2,2,6,6-tetramethylpiperidine (2.5 mL, 14.96 mmol) and anhydrous THF (25 mL) under a nitrogen atmosphere. The contents were cooled to −78° C. and n-butyllithium (2.5 M in hexane, 5.7 mL, ˜14.28 mmol) was added dropwise over a 5 minute period. The reaction mixture was stirred at −78° C. for 5 minutes, bought to 0° C. and stirred at 0° C. for 25 minutes. The reaction mixture was recooled to −78° C. and 2-chloropyrazine (0.78 g, 1 mL, 6.8 mmol) was added over a 3 minute period. After 30 minutes at −78° C., anhydrous DMF (0.99 mL, 13.6 mmol) was added over 3 minutes and the contents stirred at −78° C. for a further 30 minutes. The reaction mixture was bought to 0° C., stirred at 0° C. for 15 minutes, recooled to −78° C. and quenched by the addition of acetic acid (4 mL) in THF (10 mL). The reaction mixture was stirred at room temperature for 10 minutes and partitioned between ethyl acetate (60 mL) and brine (30 mL). The ethyl acetate layer is separated, dried over sodium sulfate, concentrated under reduced pressure and purified by silica gel flash chromatography using dichloromethane and ethyl acetate (9.5:0.5, 400 mL) to yield the title compound a (950 mg). 1H-NMR of the compound was consistent with the desired structure.

1. customA flame dried
2. temperaturecooled 100 mL round bottom flask
3. custombought to 0° C.
4. stirringstirred at 0° C. for 25 minutes
5. customwas recooled to −78° C.
6. waitAfter 30 minutes at −78° C.
7. stirringthe contents stirred at −78° C. for a further 30 minutes
8. customwas bought to 0° C.
9. stirringstirred at 0° C. for 15 minutes
10. customrecooled to −78° C.
11. customquenched by the addition of acetic acid (4 mL) in THF (10 mL)
12. stirringThe reaction mixture was stirred at room temperature for 10 minutes
13. custompartitioned between ethyl acetate (60 mL) and brine (30 mL)
14. customThe ethyl acetate layer is separated
15. dry with materialdried over sodium sulfate
16. concentrationconcentrated under reduced pressure
17. custompurified by silica gel flash chromatography

ORD record

ord-a950994d34004e21a05cc0bd692104de

Source dataset

uspto-grants-2012_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08309571B2