Methyl chloroformate → Methyl 6-chloro-2-fluoronicotinate

Temperature

0 °C

2-Chloro-6-fluoropyridine (298 mg, 2.3 mmol) was taken up in tetrahydrofuran (11.4 mL) and cooled to −78° C. n-Butyllithium (1.42 mL of 1.6 M in hexanes, 2.3 mmol) was added dropwise over 5 min. The solution was stirred for 30 minutes and methyl chloroformate (0.3 mL, 3.9 mmol) was added dropwise over 15 minutes. The resulting mixture was stirred at −78° C. for 2 hrs and then warmed to 0° C. and stirred for 3 hours. The reaction was then quenched with saturated aqueous ammonium chloride and extracted 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 as a white solid.

1. additionwas added dropwise over 5 min
2. stirringThe resulting mixture was stirred at −78° C. for 2 hrs
3. stirringstirred for 3 hours
4. customThe reaction was then quenched with saturated aqueous ammonium chloride
5. extractionextracted with ethyl acetate
6. dry with materialThe combined organics were dried over magnesium sulfate
7. filtrationfiltered
8. concentrationconcentrated in vacuo
9. customThe crude residue was purified by flash chromatography (silica, 0-17% ethyl acetate/hexanes)

ORD record

ord-492192bc6991409b9adde6fd4539fc88

Source dataset

uspto-grants-2013_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08367706B2