Reaktion #414348

Reaktionsgleichung

water

thionyl chloride

3,3,3-trifluoro-2-hydroxy-2-methylpropanoic acid

4-Amino-4'-fluorobenzophenone

→

propanamide

Ausbeute 58.0%

N-[4-(4-Fluorophenylcarbonyl)phenyl]-3,3,3-trifluoro-2-hydroxy-2-methyl propanamide

Ausbeute 58.0%

Lösungsmittel

methylene chloride

hexane

N,N-dimethylacetamide

Reaktionsbedingungen

Aufarbeitung

1. 1
   workup.STIRRINGthe reaction mixture stirred at room temperature overnight
2. 2
   Sonstigethe cloudy solution decanted from a gum
3. 3
   Filtrationfiltered through a thin pad of Celite
4. 4
   WaschenThe Celite was washed with methylene chloride
5. 5
   workup.ADDITIONthe solution added to a solution of the gum in methylene chloride
6. 6
   TrocknenThe combined methylene chloride solution was dried (MgSO4)
7. 7
   Filtrationfiltered
8. 8
   Sonstigethe solvent removed
9. 9
   Sonstigeto yield an oil
10. 10
    workup.DISSOLUTIONto dissolve the oil
11. 11
    SonstigeThe solution volume was reduced slightly on a steam bath
12. 12
    Temperaturthe solution cooled
13. 13
    Sonstigeformed
14. 14
    workup.WAITthe mixture refrigerated for several hours
15. 15
    Filtrationthe resulting solid filtered off
16. 16
    SonstigeThe 1.60 g of impure product was further purified by chromatography on 80 g of flash column silica gel
17. 17
    workup.DISSOLUTIONthe residual oil dissolved in 15 mL of methylene chloride
18. 18
    workup.ADDITIONadded to 250 mL of rapidly stirred hexane
19. 19
    SonstigeThe resulting solid was collected
20. 20
    Sonstigedried

Vorschrift

To a stirred, cooled (-20° C.) solution of 3,3,3-trifluoro-2-hydroxy-2-methylpropanoic acid (1.58 g, 10 mmol) in N,N-dimethylacetamide (15 mL) was added thionyl chloride (1.25 g, 10.5 mmol) and the mixture stirred at -20° to -5° C. for 1 hour. 4-Amino-4'-fluorobenzophenone (1.44 g, 6.7 mmol) was added in one portion and the reaction mixture stirred at room temperature overnight. The reaction mixture was poured into water, the cloudy solution decanted from a gum and filtered through a thin pad of Celite. The Celite was washed with methylene chloride and the solution added to a solution of the gum in methylene chloride. The combined methylene chloride solution was dried (MgSO4), filtered and the solvent removed to yield an oil. The oil was treated with 50 mL of hexane and enough methylene chloride to dissolve the oil. The solution volume was reduced slightly on a steam bath and the solution cooled and scratched until crystals formed. The volume was reduced further on the steam bath, the mixture refrigerated for several hours and the resulting solid filtered off. The 1.60 g of impure product was further purified by chromatography on 80 g of flash column silica gel using ethyl ether as eluent. The solvent was stripped from the first 150 mL of eluent, the residual oil dissolved in 15 mL of methylene chloride and added to 250 mL of rapidly stirred hexane. The resulting solid was collected and dried to yield the title propanamide (0.22 g, 58%) as a pale yellow solid; mp 131°-133° C. 1H--NMR (250 MHz, CDCl3): 1.77 (s, 3H, CH3), 4.09 (s, 1H, OH), 7.14-7.28 (m, 2H,aromatic), 7.69-7.85 (m, 6H, aromatic), 8.68 (s, 1H, NH). MS (CI, CH4): 356M+1).

Quelle