Triethylamine → 3-[N-(4-Fluoro-2-trifluoromethylphenyl)sulfamoyl]-benzoic acid-[2-hydroxy-2-(2,2-dimethyl-1,3-dioxolan-4-yl)-ethylamide]

HRID 654016Notes

Reaction equation

HRID 654016 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][S:9]([C:12]2[CH:13]=[C:14]([CH:18]=[CH:19][CH:20]=2)[C:15](O)=[O:16])(=[O:11])=[O:10])=[C:4]([C:21]([F:24])([F:23])[F:22])[CH:3]=1.S(Cl)(Cl)=O.C(N(CC)CC)C.[OH:36][CH:37]([CH:40]1[CH2:44][O:43][C:42]([CH3:46])([CH3:45])[O:41]1)[CH2:38][NH2:39]>C(OCC)(=O)C>[OH:36][CH:37]([CH:40]1[CH2:44][O:43][C:42]([CH3:46])([CH3:45])[O:41]1)[CH2:38][NH:39][C:15](=[O:16])[C:14]1[CH:18]=[CH:19][CH:20]=[C:12]([S:9](=[O:11])(=[O:10])[NH:8][C:5]2[CH:6]=[CH:7][C:2]([F:1])=[CH:3][C:4]=2[C:21]([F:22])([F:23])[F:24])[CH:13]=1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 24386Thionyl ChlorideHCID 11971028alpha-(Aminomethyl)-2,2-dimethyl-1,3-dioxolane-4-methanolHCID 150576143-[N-(4-fluoro-2-trifluoromethylphenyl)sulfamoyl]-benzoic acid

Product 1

HCID 150576153-[N-(4-Fluoro-2-trifluoromethylphenyl)sulfamoyl]-benzoic acid-[2-hydroxy-2-(2,2-dimethyl-1,3-dioxolan-4-yl)-ethylamide]

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

3.63 g (10 mmol) of 3-[N-(4-fluoro-2-trifluoromethylphenyl)sulfamoyl]-benzoic acid is suspended in 36 ml of ethyl acetate, 2.38 g (20 mmol) of thionylchloride is added and the suspension is heated to boiling temperature. After 15 minutes, a clear solution is present, after 1 hour the formation of the acid chloride is complete. The solution is evaporated to dryness under reduce pressure, the residue is concentrated by evaporation in a vacuum twice with 50 ml of dichloromethane each and then dissolved in 36 ml of dioxane. 1.21 g (12 mmol) of triethylamine and 1.93 g (12 mmol) of 2-hydroxy-2-(2,2-dimethyl-I,3-dioxolan-4-yl)-ethylamine are added to this solution and it is stirred for 5 hours at room temperature. The reaction mixture is then evaporated to dryness in a vacuum, the residue is extracted with ethyl acetate, the ethyl acetate extract is concentrated by evaporation in a vacuum and the residue is chromatographed on silica gel 60 (Merck) with ethyl acetate/hexane. 3.42 g (6.75 mmol) =67.5% of the theoretical yield of the product is obtained as an amorphous solid.

Workup

  1. temperaturethe suspension is heated
  2. waita clear solution is present, after 1 hour
  3. customThe solution is evaporated to dryness
  4. concentrationthe residue is concentrated by evaporation in a vacuum twice with 50 ml of dichloromethane each and
  5. dissolutionthen dissolved in 36 ml of dioxane
  6. customThe reaction mixture is then evaporated to dryness in a vacuum
  7. extractionthe residue is extracted with ethyl acetate
  8. extractionthe ethyl acetate extract
  9. concentrationis concentrated by evaporation in a vacuum
  10. customthe residue is chromatographed on silica gel 60 (Merck) with ethyl acetate/hexane
  11. custom3.42 g (6.75 mmol) =67.5% of the theoretical yield of the product is obtained as an amorphous solid

Sources & evidence

ORD record
ord-c7cb55b0a3ff4b12951c5014a976409f
Source dataset
uspto-grants-1992_07
Patent number
US05130119

Reaction notes

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