Hydrochloric Acid → N-[2-(4-Fluorophenyl)-2-oxoethyl]formamide

To a solution of α-bromo-4-fluoroacetophenone (30.0 g, 0.138 mol) in N,N-dimethylformamide (200 ml) was added sodium azide (8.99 g, 0.136 mol) under ice-cooling and the mixture was stirred under ice-cooling for 30 min. After diluting the reaction solution with water, the solution was extracted with ethyl acetate. The extract was washed successively with water and saturated brine, dried over magnesium sulfate and concentrated under reduced pressure. The residue was dissolved in methanol (300 ml). 10% Pd/C (containing water by 50%, 3.0 g) and conc. hydrochloric acid (12.7 ml, 0.152 mol) were added and the mixture was stirred under hydrogen stream for 21 hrs. The catalyst was filtered off and the reaction solution was concentrated under reduced pressure. A mixed solution of sodium formate (10.3 g, 0.152 mol), acetic anhydride (140 ml) and formic acid (70 ml) was added to the residue and the mixture was stirred at room temperature for 1 hr. The reaction solution was concentrated under reduced pressure, diluted with water, and extracted with ethyl acetate. The extract was washed with saturated brine, dried over magnesium sulfate and concentrated under reduced pressure. The residue was recrystallized from ethyl acetate-hexane to give the objective substance (20.21 g, 81%) as crystals.

1. temperaturecooling
2. temperaturecooling for 30 min
3. extractionthe solution was extracted with ethyl acetate
4. washThe extract was washed successively with water and saturated brine
5. dry with materialdried over magnesium sulfate
6. concentrationconcentrated under reduced pressure
7. dissolutionThe residue was dissolved in methanol (300 ml)
8. stirringthe mixture was stirred under hydrogen stream for 21 hrs
9. filtrationThe catalyst was filtered off
10. concentrationthe reaction solution was concentrated under reduced pressure
11. stirringthe mixture was stirred at room temperature for 1 hr
12. concentrationThe reaction solution was concentrated under reduced pressure
13. additiondiluted with water
14. extractionextracted with ethyl acetate
15. washThe extract was washed with saturated brine
16. dry with materialdried over magnesium sulfate
17. concentrationconcentrated under reduced pressure
18. customThe residue was recrystallized from ethyl acetate-hexane
19. customto give the objective substance (20.21 g, 81%) as crystals

ORD record

ord-9b5750ffae7940b499213282b51b99eb

Source dataset

uspto-grants-2006_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06982348B2