反应详情

温度

-78 °C

A portion of the 4-bromo-2,5-dimethylpyridine (15.4 g, 83.0 mmol) was dissolved in 500 mL of anhydrous diethyl ether and chilled to -78° C. n-Butyllithium (52 mL, 1.6M in hexanes) was added dropwise and the resulting slurry was stirred for 30 minutes. 4-(3-((tert-butyldimethylsilyl)oxy)benzoyl)-N,N-diethylbenzamide (34.2 g, 83.0 mmol) was dissolved in 250 mL of anhydrous diethyl ether and chilled to -78° C. The lithiated pyridine was slowly transferred via cannula to the diarylketone solution. The temperature was allowed to rise to -40° C. for 4.5 hours. The reaction was quenched with saturated aqueous ammonium chloride. The diethyl ether layer was separated, the solvent was removed, and the residue was redissolved in 300 mL acetonitrile. Tetraethylammonium fluoride hydrate (19.8 g) was added, and the reaction was stirred overnight. The solvent was removed, and the residue was redissolved in 500 mL 1M hydrochloric acid and washed with 500 mL of diethyl ether. The pH of the aqueous solution was adjusted to 8 and the solution was extracted with dichloromethane. The solvent was removed and the residue was crystallized from acetonitrile to give 16.4 g (48%) of (±)-4-(α-(2,5-dimethyl-4-pyridyl)-α,3-dihydroxybenzyl)-N,N-diethylbenzamide.

1. additionwas added dropwise
2. waitto rise to -40° C. for 4.5 hours
3. customThe reaction was quenched with saturated aqueous ammonium chloride
4. customThe diethyl ether layer was separated
5. customthe solvent was removed
6. dissolutionthe residue was redissolved in 300 mL acetonitrile
7. additionTetraethylammonium fluoride hydrate (19.8 g) was added
8. stirringthe reaction was stirred overnight
9. customThe solvent was removed
10. dissolutionthe residue was redissolved in 500 mL 1M hydrochloric acid
11. washwashed with 500 mL of diethyl ether
12. extractionthe solution was extracted with dichloromethane
13. customThe solvent was removed
14. customthe residue was crystallized from acetonitrile