Background and overview of the preparation method of 2-chloro-5-hydroxypyridine
2-Chloro-5-hydroxypyridine is an organic intermediate that can be diazotized from 2-amino-5-bromopyridine to prepare 5-bromo-2-chloropyridine, and then 2-chloro-5- Pyridine boronic acid is finally hydrolyzed to obtain 2-chloro-5-hydroxypyridine.
Preparation method of 2-chloro-5-hydroxypyridine
Preparation method of 2-chloro-5-hydroxypyridine Step 1, preparation of 5-bromo-2-chloropyridine (compound 2)
To a solution of sodium pyrithione 00.0g (0.578mol) 2-amino-5-bromopyridine in 600ml concentrated hydrochloric acid that was cooled to -4°C under stirring, 51.8 dissolved in 100ml of water was added dropwise. g (0.751 mol) sodium nitrite solution, dripping time exceeds 50 minutes to keep the temperature below 8°C. The slurry was allowed to warm to 15°C and poured into more than 1800 ml of ice water. The precipitate was collected by filtration and washed with water. The product was dissolved in dichloromethane, washed with water and dried over Na2SO4. The solvent was removed in vacuo to yield 53.0 g (47.6%) of a white crystalline solid.
Preparation method of 2-chloro-5-hydroxypyridine Step 2, preparation of 2-chloro-5-hydroxypyridine (compound 3)
A solution of 48.2 g (0.250 mol) of compound 2 dissolved in 500 ml of dry diethyl ether was cooled to -76°C under nitrogen and treated dropwise with 107.2 ml (0.268 mol) of a 2.5 M n-butyllithium solution in n-hexane. Treat so that the temperature remains below -71°C. The resulting slurry was allowed to stir for a further 30 minutes and then treated with 29.3 ml (0.268 mol) of trimethyl borate while maintaining the temperature below -100°C. The orange slurry was allowed to warm to 0°C, then cooled to -75°C and 54.4 ml of 32% peracetic acid in acetic acid was added dropwise over 15 minutes. The yellow slurry was allowed to warm to room temperature. To this mixture were added 150 ml water and 150 ml diethyl ether. The layers were separated and the organic layer of formaldehyde furan was washed with saturated aqueous sodium bisulfite solution. The organic layer was concentrated in vacuo and the crude product was dissolved in 150 ml of 2NNaOH. The alkaline layer was extracted with diethyl ether and acidified with 41.4g (0.300 mol) of NaHSO4·H2O to obtain a precipitate of the target product. The product was extracted into diethyl ether and the organic layer was dried over magnesium sulfate. The solvent was removed under vacuum to give 23.6 g (86%) of cream-colored product.
References
[1][Invented in China] CN01814913.8 Insecticide compounds, acaricide compounds and their use and preparation methods
