ChemicalBook CAS DataBase List 2,4-Dichloropyridine-3-carboxylic acid

2,4-Dichloropyridine-3-carboxylic acid synthesis

6synthesis methods

Product Name:2,4-Dichloropyridine-3-carboxylic acid
CAS Number:262423-77-8
Molecular formula:C6H3Cl2NO2
Molecular Weight:192

124-38-9
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262423-77-8
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$9.00/1g

Yield:262423-77-8 82%

Reaction Conditions:

Stage #1:2,4-dichloropyridine with n-butyllithium;N-ethyl-N,N-diisopropylamine in tetrahydrofuran;hexane at -78; for 0.5 h;
Stage #2:carbon dioxide in tetrahydrofuran;hexane at -78 - 20; for 0.166667 h;
Stage #3: with hydrogenchloride;water; pH=4

Steps:

Preparation of 2,4-Dichloronicotinic acid To a stirring solution of diisopropyl ethyl amine (11.1 ml, 81.08 mmol) in THF (50 ml) was added dropwise a solution of BuLi (1.46 M, 43.3 ml, 73.65 mmol) in hexane below -65° C. and the mixture was stirred for 40 minutes. To this solution was added dropwise 2,4-dichloropyridine (10 g, 67.57 mmol) in THF (15 mL) at -78° C. and stirred for 30 minutes. Carbon dioxide generated from freshly crushed dry ice was passed through CaCl₂ guard tube and then charged into the reaction mixture for 10 minutes and the reaction mixture was slowly allowed to come to room temperature. The solvent was evaporated under reduced pressure and dissolved in a minimum volume of water. The aqueous layer was washed with water and acidified to pH 4 with conc. HCl. It was then extracted with ethyl acetate, the organic layer was washed with brine and dried over sodium sulfate. The organic solvent was removed under reduced pressure to provide 2,4-dichloronicotinic acid (10.6 g, 82%) as off white solid. ¹H NMR (400 MHz, DMSO-d₆): δ 14.88-14.54 (br s, 1H), 8.46 (d, J=5.3 Hz, 1H), 7.74 (d, J=5.5 Hz, 1H). FIA MS [M+H]: 191.8

References:

Pfizer Inc US2008/85887, 2008, A1 Location in patent:Page/Page column 17

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