Carbon Dioxide → 2-Chloro-6-(trifluoromethyl)pyridine-4-carboxylic acid

Temperature

-75 °C

To a stirred solution of 1.1 g of 2-chloro-4-iodo-6-trifluoromethyl-pyridine (3.58 mmol) in 15 ml THF under argon at −75° C., were added 2.2 ml of n-BuLi (1.6 M in hexane) within 15 min (temperature kept between −72° C. and −75° C.). After 5 additional min stirring at −75° C., the reaction mixture was poured on an excess of freshly crushed dry ice and stirred until RT was reached. The reaction mixture was then concentrated in vacuo, the remaining residue treated with 2M aqueous HCl and the resulting mixture was extrated with diethylether. The combined organic phases were washed with water, and then extracted with saturated NaHCO3 solution. The aqueous phase was then acidified with concentrated HCl, extracted twice with diethylether and the combined organic phases were washed with brine, dried over magnesium sulfate, filtered and concentrated in vacuo. The remaining residue was recrystalized from 12 ml hot n-hexane, leading to 0.459 g (56%) of 2-chloro-6-trifluoromethyl-isonicotinic acid as an off-white solid. MS: 224.0 (M−H)−.

1. stirringstirred until RT
2. concentrationThe reaction mixture was then concentrated in vacuo
3. additionthe remaining residue treated with 2M aqueous HCl
4. washThe combined organic phases were washed with water
5. extractionextracted with saturated NaHCO3 solution
6. extractionextracted twice with diethylether
7. washthe combined organic phases were washed with brine
8. dry with materialdried over magnesium sulfate
9. filtrationfiltered
10. concentrationconcentrated in vacuo
11. customThe remaining residue was recrystalized from 12 ml hot n-hexane

ORD record

ord-608d7cbc072242ad8eab9c2fa3c2055a

Source dataset

uspto-grants-2010_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07745477B2