Hydrochloric Acid → HCID 67975084, compound

To a solution of 5-bromo-3-chloro-2,4-dimethylpyridine 1-oxide (373 mg; 1.5772 mmol) in dichloromethane (10 mL; 156.0 mmol) was added trifluoroacetic anhydride (0.70 mL; 5.0 mmol). The reaction mixture was stirred at room temperature for 20 hours. Trifluoroacetic anhydride (0.5 mL; 4 mmol) was then added and the reaction mixture stirred for an additional 4 hours at room temperature. The reaction mixture was poured into 2M aqueous potassium carbonate and extracted twice with dichloromethane. The combined dichloromethane extracts were dried over magnesium sulfate, filtered, and evaporated in vacuo. The resulting residue was dissolved in tetrahydrofuran (6 mL), and treated with sodium hydroxide (10 mol/L) in water (0.60 mL; 6.0 mmol). The mixture was stirred at room temperature for 2 hours, and then neutralized with 5M aqueous HCl (1.3 mL). The reaction mixture was poured into saturated aqueous sodium bicarbonate and extracted with dichloromethane (3×100 mL). The combined organic extracts were dried over magnesium sulfate, filtered, and concentrated. The crude product was purified via flash chromatography on silica gel (24 g silica, solvent gradient: 20-100% ethyl acetate in dichloromethane) to yield 255.6 mg (69%) of the title compound. LCMS (ESI): M+H=236.2; 1H NMR (400 MHz, CDCl3) δ 8.55 (s, 1H), 4.73 (d, J=4.8 Hz, 2H), 4.05 (s, 1H), 2.55 (s, 3H).

1. stirringthe reaction mixture stirred for an additional 4 hours at room temperature
2. extractionextracted twice with dichloromethane
3. dry with materialThe combined dichloromethane extracts were dried over magnesium sulfate
4. filtrationfiltered
5. customevaporated in vacuo
6. dissolutionThe resulting residue was dissolved in tetrahydrofuran (6 mL)
7. stirringThe mixture was stirred at room temperature for 2 hours
8. extractionextracted with dichloromethane (3×100 mL)
9. dry with materialThe combined organic extracts were dried over magnesium sulfate
10. filtrationfiltered
11. concentrationconcentrated
12. customThe crude product was purified via flash chromatography on silica gel (24 g silica, solvent gradient: 20-100% ethyl acetate in dichloromethane)

ORD record

ord-8b9c83625a3e4ee0aff3c4460835465c

Source dataset

uspto-grants-2015_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09206175B2