Carbon Dioxide → 3,5-Dichloroisonicotinic acid

Diisopropylamine (31 mL, 221 mmol) was dissolved in tetrahydrofuran (200 mL), and the solution was added drop-wisely with a 1.6 mol/L hexane solution of n-butyllithium (128 mL, 205 mmol) at −78° C. The mixture was stirred for 15 minutes, and was added drop-wisely with a tetrahydrofuran solution (200 mL) of 3,5-dichloropyridine (25.1 g, 170 mmol) while keeping the temperature at −78° C., and then stirred for additional 1 hour. The reaction solution was added with dry ice to thereby gradually heat to room temperature, and further stirred for 15 hours. The mixture was treated with water (1 L), added with a 1 mol/L aqueous sodium hydroxide solution (100 mL), and washed with ether. The separated aqueous phase was adjusted to be acidic using a 6 mol/L hydrochloric acid, and the resultant precipitate was collected by filtration. The filtrate was extracted with ethyl acetate, the extract was dried over anhydrous sodium sulfate, evaporated under reduced pressure so as to remove the solvent, and the mixture of the resultant residue and the precipitate previously collected were re-crystallized from ethanol, which yielded 3,5-dichloropyridine-4-carboxylic acid (yield: 23 g, yield ratio: 70%) as a yellow crystal.

1. customat −78° C.
2. stirringstirred for additional 1 hour
3. stirringfurther stirred for 15 hours
4. washwashed with ether
5. filtrationthe resultant precipitate was collected by filtration
6. extractionThe filtrate was extracted with ethyl acetate
7. dry with materialthe extract was dried over anhydrous sodium sulfate
8. customevaporated under reduced pressure so as
9. customto remove the solvent
10. additionthe mixture of the resultant residue
11. customthe precipitate previously collected
12. customwere re-crystallized from ethanol, which

ORD record

ord-42aad39ce09140098b59d3fa2bf85854

Source dataset

uspto-grants-2008_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07335673B2