Carbon Dioxide → N-[4-(2-Pyridyl)sulfonylphenyl]-3,3,3-trifluoro-2-hydroxy-2-trifluoromethyl-propanamide

HRID 327210Notes

Reaction equation

HRID 327210 reaction equation
[F:1][C:2]([F:13])([F:12])[C:3]([C:8]([F:11])([F:10])[F:9])([OH:7])[C:4](O)=[O:5].C(N1C=CN=C1)(N1C=CN=C1)=O.C(=O)=O.[N:29]1[CH:34]=[CH:33][CH:32]=[CH:31][C:30]=1[S:35]([C:38]1[CH:43]=[CH:42][C:41]([NH2:44])=[CH:40][CH:39]=1)(=[O:37])=[O:36]>CN(C)C=O.C(Cl)(Cl)Cl.CO.O1CCCC1>[N:29]1[CH:34]=[CH:33][CH:32]=[CH:31][C:30]=1[S:35]([C:38]1[CH:43]=[CH:42][C:41]([NH:44][C:4](=[O:5])[C:3]([OH:7])([C:8]([F:11])([F:10])[F:9])[C:2]([F:13])([F:12])[F:1])=[CH:40][CH:39]=1)(=[O:36])=[O:37]

Participants

8

Reactant 4

HCID 280Carbon DioxideHCID 682631,1'-Carbonyldiimidazole2×HCID 27250433,3,3-Trifluoro-2-hydroxy-2-(trifluoromethyl)propionic Acid2×HCID 105138504-(2-Pyridylsulfonyl)aniline

Product 1

HCID 21480099N-[4-(2-Pyridyl)sulfonylphenyl]-3,3,3-trifluoro-2-hydroxy-2-trifluoromethyl-propanamideYield 18.8%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolventHCID 21584188Chloroform methanolSolvent

Conditions

Temperature
35 °C

Procedure

Tetrahydrofuran (5 ml, dry) was added to a mixture of 2,2-bis-trifluoromethyl-2-hydroxyacetic acid (0.98 g, 4.6 mmol) and 1,1'-carbonyldiimidazole (0.75 g, 4.6 mmol), while under a nitrogen atmosphere. There was an immediate evolution of carbon dioxide. The reaction was heated at 35° C. in an ultra-sound bath for 15 mins. The reaction was treated with a solution of 4-(2-pyridylsulfonyl)benzeneamine (1.08 g, 4.6 mmol) in dimethylformamide (11 ml, dry), heated at 46° C. for 18 hr, and then 60° C. for 24 hr. The incomplete reaction was treated with a solid mixture of 2,2-bis-trifluoromethyl-2-hydroxyacetic acid (0.22 g, 1.0 mmol) and 1,1'-carbonyldiimidazole (0.20 g, 1.2 mmol), and heated to 52° C. in an ultrasound bath for 18 hr. The reaction was evaporated to a viscous gold liquid, which was treated with water (100 ml) and extracted with ethyl acetate (2×100 ml). The combined organic portions were dried (MgSO4) and evaporated to yield a gold oil. Chromatography of this oil on silica gel eluting with chloroform/methanol (98:2) provided the title compound (0.37 g, 14%) as a white solid; mp 199°-200° C. 1H--NMR (250 MHz, d6 --DMSO): 7.70 (m, 1H, ArH), 8.02 (m, 4H, ArH), 8.19 (m, 2H, ArH), 8.71 (d, J=4.0 Hz, 1H, ArH), 9.88 (s, 1H, OH), 10.94 (s, 1H, NH). MS(CI,CH4) 429 (M+1)

Workup

  1. temperatureheated at 46° C. for 18 hr
  2. customThe incomplete reaction
  3. temperatureheated to 52° C. in an ultrasound bath for 18 hr
  4. customThe reaction was evaporated to a viscous gold liquid, which
  5. additionwas treated with water (100 ml)
  6. extractionextracted with ethyl acetate (2×100 ml)
  7. dry with materialThe combined organic portions were dried (MgSO4)
  8. customevaporated
  9. customto yield a gold oil

Sources & evidence

ORD record
ord-6fa1a28b9b274ed28d51410c5e5f2272
Source dataset
uspto-grants-1993_12
Patent number
US05272163

Reaction notes

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