Hydrochloric Acid → 5-fluoro-N-methoxy-N,3-dimethyl-1-benzofuran-2-carboxamide

Temperature

80 °C

To a mixture of 1-(5-fluoro-2-hydroxyphenyl)ethanone (10.0 g), 2-chloro-N-methoxy-N-methylacetamide (9.82 g), sodium iodide (19.5 g) and N,N-dimethylformamide (200 mL) was added potassium carbonate (18.0 g), and the mixture was stirred at 80° C. overnight. 1N Hydrochloric acid was added to quench the reaction, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure to give a brown solid. To a solution (200 mL) of the obtained solid in N,N-dimethylformamide was added 1,8-diazabicyclo[5.4.0]undec-7-ene (9.71 mL), and the mixture was stirred at 120° C. for 4 hr. 1N Hydrochloric acid was added to quench the reaction, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate:hexane=1:3, volume ratio) to give the title object compound (4.37 g, 28%) as a brown oil.

1. customto quench
2. customthe reaction
3. extractionthe mixture was extracted with ethyl acetate
4. washThe extract was washed with saturated brine
5. dry with materialdried over magnesium sulfate
6. concentrationconcentrated under reduced pressure
7. customto give a brown solid
8. stirringthe mixture was stirred at 120° C. for 4 hr
9. customto quench
10. customthe reaction
11. extractionthe mixture was extracted with ethyl acetate
12. washThe extract was washed with saturated brine
13. dry with materialdried over magnesium sulfate
14. concentrationconcentrated under reduced pressure
15. customThe residue was purified by silica gel column chromatography (ethyl acetate:hexane=1:3, volume ratio)

ORD record

ord-33389889aee84fd5a07f48b88e586dbe

Source dataset

uspto-grants-2013_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08436043B2