反応 #414340

反応方程式

HCl

thionyl chloride

3,3,3-trifluoro-2-hydroxy-2-methyl propanoic acid

4-(2-Methylphenylsulfonyl)benzenamine

→

propanamide

収率 77.0%

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

収率 77.0%

溶媒

N,N-dimethylacetamide

反応条件

後処理

1. 1
   その他the mixture (a precipitate formed after a few minutes)
2. 2
   洗浄washed in with 2 mL of N,N-dimethylacetamide
3. 3
   workup.STIRRINGto stir at room temperature overnight
4. 4
   workup.ADDITIONThe solution was poured into water
5. 5
   その他the cloudy solution decanted from the resulting gum
6. 6
   ろ過filtered through a thin pad of Celite
7. 7
   洗浄The Celite pad was washed with methylene chloride
8. 8
   workup.ADDITIONthe solution added to a solution of the gum in methylene chloride
9. 9
   乾燥The combined methylene chloride solution was dried (MgSO4)
10. 10
    ろ過filtered
11. 11
    その他the solvent removed in vacuo
12. 12
    workup.DISSOLUTIONThe resulting gum was dissolved in a few mL of methanol
13. 13
    workup.ADDITIONadded dropwise to 100 mL of rapidly stirred 3N HCl
14. 14
    その他The aqueous phase was decanted from the gum
15. 15
    workup.DISSOLUTIONthe gum dissolved in methylene chloride
16. 16
    乾燥dried (MgSO4)
17. 17
    ろ過filtered
18. 18
    その他the solvent removed in vacuo
19. 19
    workup.DISSOLUTIONThe residue was dissolved in 125 mL of methylene chloride
20. 20
    温度heated on a steam bath as 100 mL of hexane
21. 21
    workup.ADDITIONwas slowly added
22. 22
    workup.ADDITIONwas added to the cloud point
23. 23
    温度After cooling overnight the resulting solid
24. 24
    ろ過was filtered
25. 25
    その他to yield impure product
26. 26
    その他the aqueous phase decanted off
27. 27
    workup.DISSOLUTIONthe residual gum dissolved in methylene chloride
28. 28
    乾燥dried (MgSO4)
29. 29
    ろ過filtered
30. 30
    その他the solvent removed in vacuo
31. 31
    workup.DISSOLUTIONThe material was dissolved in 100 mL of methylene chloride
32. 32
    workup.ADDITION50 mL of hexane added
33. 33
    温度the solution heated on a steam bath to a final volume of 100 mL
34. 34
    温度After cooling the resulting solid
35. 35
    ろ過was filtered
36. 36
    その他dried at 100-120° C./0.1 torr

実験手順

To a stirred, cooled (-15° C.) solution of 3,3,3-trifluoro-2-hydroxy-2-methyl propanoic acid (1.42 g, 9.0 mmol) in N,N-dimethylacetamide (13 mL) was rapidly added thionyl chloride (1.13 g, 9.5 mmol) and the mixture (a precipitate formed after a few minutes) stirred at -20° C. to -10° C. for 1 hour. 4-(2-Methylphenylsulfonyl)benzenamine (1.48 g, 6.0 mmol) was then added in one portion, washed in with 2 mL of N,N-dimethylacetamide and the mixture allowed to stir at room temperature overnight. The solution was poured into water, the cloudy solution decanted from the resulting gum and filtered through a thin pad of Celite. The Celite pad 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 in vacuo. The resulting gum was dissolved in a few mL of methanol and added dropwise to 100 mL of rapidly stirred 3N HCl. The aqueous phase was decanted from the gum, the gum dissolved in methylene chloride, dried (MgSO4) filtered and the solvent removed in vacuo. The residue was dissolved in 125 mL of methylene chloride and heated on a steam bath as 100 mL of hexane was slowly added to replace the methylene chloride. When a volume of 125 mL was reached more hexane (ca. 50 mL) was added to the cloud point. After cooling overnight the resulting solid was filtered to yield impure product. This material was further stirred with 300 mL of 0.5N HCl for 45 min., the aqueous phase decanted off and the residual gum dissolved in methylene chloride, dried (MgSO4), filtered and the solvent removed in vacuo. The material was dissolved in 100 mL of methylene chloride, 50 mL of hexane added and the solution heated on a steam bath to a final volume of 100 mL. After cooling the resulting solid was filtered and dried at 100-120° C./0.1 torr. for 2.5 hours to yield the title propanamide (1.78 g, 77%) as a light tan solid; mp 126°-128° C. 1H--NMR (300 MHz, d6 --DMSO): 1.58 (s, 3H, CH3), 2.39 (s, 3H, aryl CH3), 7.37-8.10 (m, 8H, aromatic), 7.6 (broad s, 1H, OH), 10.4 (broad s, 1H, NH). MS (CI, CH4): 388(M+1).

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