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

HRID 865274Notes

Reaction equation

HRID 865274 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][C:32]([S:35]([C:38]2[CH:43]=[CH:42][C:41]([NH2:44])=[CH:40][CH:39]=2)(=[O:37])=[O:36])=[CH:31][CH:30]=1>CN(C)C=O.O.O1CCCC1>[N:29]1[CH:30]=[CH:31][C:32]([S:35]([C:38]2[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]=2)(=[O:37])=[O:36])=[CH:33][CH:34]=1

Participants

8

Reactant 4

HCID 280Carbon DioxideHCID 682631,1'-CarbonyldiimidazoleHCID 4595324-Sulfanilylpyridine2×HCID 27250433,3,3-Trifluoro-2-hydroxy-2-(trifluoromethyl)propionic Acid

Product 1

HCID 21480139N-[4-(4-Pyridylsulfonyl)phenyl]-3,3,3-trifluoro-2-hydroxy-2-trifluoromethyl-propanamideYield 6%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
35 °C

Procedure

Tetrahydrofuran (5 ml,dry) was added to a mixture of 2,2-bis-trifluoromethyl-2-hydroxyacetic acid (1.29 g, 6.1 mmol) and 1,1'carbonyldiimidazole (0.99 g, 6.1 mmol), while under a nitrogen atmosphere. There was an immediate evolution of carbon dioxide. The reaction was heated at 35° C. for 15 min. The reaction was treated with a solution of 4-(4-pyridylsulfonyl)benzeneamine (1.43 g, 6.1 mmol) in dimethylformamide (15 ml,dry), and heated to 69° C. in an ultrasonic bath for 19.5 hrs. The reaction was poured into water (300 ml), and extracted with ethyl ether (3×300 ml). The combined organic portions were evaporated and preabsorbed onto silica gel (10 gm). Chromatography of this material on silica gel, eluting with methylene chloride/ethyl acetate (first 100:0 and then 70:30) provided a white solid. Recrystallization from acetone gave starting 4-(4-pyridylsulfonyl)benzeneamine. The filtrate was evaporated and chromatographed on silca gel eluting with chloroform/methanol (first 100:0 and then 98:2) provided the title compound (0.115 g, 6%) as a white solid; mp 235°-237° C. 1H-NMR (250 MHz,d6 -DMSO): 7.90 (d, J=4.6, 2H, ArH), 8.04 (d, 4H, ArH), 8.89 (d, J=4.68 Hz, 2H, ArH), 9.90 (s, 1H, OH), 10.97 (s, 1H, NM). MS(CI,CH4): 429 (M+1)

Workup

  1. temperatureheated to 69° C. in an ultrasonic bath for 19.5 hrs
  2. extractionextracted with ethyl ether (3×300 ml)
  3. customThe combined organic portions were evaporated
  4. custompreabsorbed onto silica gel (10 gm)
  5. washChromatography of this material on silica gel, eluting with methylene chloride/ethyl acetate (first 100:0
  6. custom70:30) provided a white solid
  7. customRecrystallization from acetone
  8. customgave
  9. customThe filtrate was evaporated
  10. customchromatographed on silca gel
  11. washeluting with chloroform/methanol (first 100:0

Sources & evidence

ORD record
ord-92235f2fd9984c76ad4b921e85afb90c
Source dataset
uspto-grants-1996_10
Patent number
US05565477

Reaction notes

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