Dimethylformamide → 6-Chloro-2-fluoronicotinaldehyde

Temperature

0 °C

Diisopropylamine (1.14 ml, 8.0 mmol) was taken up in 8 mL tetrahydrofuran and cooled to −78° C. n-Buyllithium (4.8 ml, 7.6 mmol) was added dropwise. The flask was then warmed to 0° C. in an ice bath and stirred for 30 minutes. The reaction mixture was then added dropwise to a cooled (−78° C.) solution of 2-chloro-6-fluoropyridine (1.0 g, 7.60 mmol) in tetrahydrofuran (25.3 ml). The reaction mixture was stirred at −78° C. for one hour. Dimethylformamide (0.88 ml, 11.4 mmol) was added dropwise and the mixture was stirred an additional 2 hours at −78° C. The reaction was quenched via the addition of 1N aqueous hydrochloric acid and allowed to warm to room temperature. The resulting biphasic mixture was extracted twice with ethyl acetate. The combined organics were dried over magnesium sulfate, filtered, and concentrated in vacuo. The crude residue was purified by flash chromatography (silica, 0-17% ethyl acetate/hexanes) to afford the title compound.

1. additionwas added dropwise
2. additionThe reaction mixture was then added dropwise to
3. stirringThe reaction mixture was stirred at −78° C. for one hour
4. stirringthe mixture was stirred an additional 2 hours at −78° C
5. customThe reaction was quenched via the addition of 1N aqueous hydrochloric acid
6. temperatureto warm to room temperature
7. extractionThe resulting biphasic mixture was extracted twice with ethyl acetate
8. dry with materialThe combined organics were dried over magnesium sulfate
9. filtrationfiltered
10. concentrationconcentrated in vacuo
11. customThe crude residue was purified by flash chromatography (silica, 0-17% ethyl acetate/hexanes)

ORD record

ord-b10895bbe26248f7b9de1106b843e40e

Source dataset

uspto-grants-2013_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08367706B2