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

HRID 654013Notes

Reaction equation

HRID 654013 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][S:9]([C:12]2[CH:20]=[CH:19][C:15]([C:16](O)=[O:17])=[CH:14][CH:13]=2)(=[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:16](=[O:17])[C:15]1[CH:14]=[CH:13][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:20][CH:19]=1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 24386Thionyl ChlorideHCID 11971028alpha-(Aminomethyl)-2,2-dimethyl-1,3-dioxolane-4-methanolHCID 150576074-[N-(4-fluoro-2-trifluoromethylphenyl)sulfamoyl]benzoic acid

Product 1

HCID 150576084-[N-(4-Fluoro-2-trifluoromethylphenyl)sulfamoyl]-benzoic acid-[2-hydroxy-2-(2,2-dimethyl-1,3-dioxolan-4-yl)-ethyl-amide]

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

3.63 g (10 mmol) of 4-[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 reduced pressure, the residue is concentrated by evaporation in a vacuum twice with 50 ml of dichloromethane each and the 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-1,3-dioxolan-4-yl)-ethylamine are added to this solution and it is stirred for 5 hours at room temperature. The reaction solution 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. 3.19 g (6.3 mmol) =63% of the theoretical yield of the product is obtained as an amorphous solid.

Workup

  1. temperaturethe suspension is heated
  2. customThe solution is evaporated to dryness under reduced pressure
  3. concentrationthe residue is concentrated by evaporation in a vacuum twice with 50 ml of dichloromethane each and the
  4. dissolutiondissolved in 36 ml of dioxane
  5. customThe reaction solution is then evaporated to dryness in a vacuum
  6. extractionthe residue is extracted with ethyl acetate
  7. extractionthe ethyl acetate extract
  8. concentrationis concentrated by evaporation in a vacuum
  9. customthe residue is chromatographed on silica gel 60 (Merck) with ethyl acetate/hexane
  10. custom3.19 g (6.3 mmol) =63% of the theoretical yield of the product is obtained as an amorphous solid

Sources & evidence

ORD record
ord-1d0ae980b6674998865f7711a5a3a508
Source dataset
uspto-grants-1992_07
Patent number
US05130119

Reaction notes

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