1,1'-Carbonyldiimidazole → N-[3-Fluoro-4-(phenylsulfonyl)phenyl]-3,3,3-trifluoro-2-hydroxy-2-trifluoromethylpropanamide

HRID 327208Notes

Reaction equation

HRID 327208 reaction equation
[F:1][C:2]([F:13])([F:12])[C:3]([OH:11])([C:7]([F:10])([F:9])[F:8])[C:4]([OH:6])=O.C(N1C=CN=C1)(N1C=CN=C1)=O.[F:26][C:27]1[CH:28]=[C:29]([NH2:42])[CH:30]=[CH:31][C:32]=1[S:33]([C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1)(=[O:35])=[O:34]>O1CCCC1>[F:26][C:27]1[CH:28]=[C:29]([NH:42][C:4](=[O:6])[C:3]([OH:11])([C:2]([F:1])([F:13])[F:12])[C:7]([F:10])([F:9])[F:8])[CH:30]=[CH:31][C:32]=1[S:33]([C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1)(=[O:35])=[O:34]

Participants

5

Reactant 3

HCID 682631,1'-CarbonyldiimidazoleHCID 27250433,3,3-Trifluoro-2-hydroxy-2-(trifluoromethyl)propionic AcidHCID 107532343-Fluoro-4-(phenyl sulfonyl)benzeneamine

Product 1

HCID 21480126N-[3-Fluoro-4-(phenylsulfonyl)phenyl]-3,3,3-trifluoro-2-hydroxy-2-trifluoromethylpropanamideYield 13.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
45 °C

Procedure

To a solution of 3,3,3-trifluoro-2-hydroxy-2-trifluoromethylpropanoic acid (1.26 g, 5.9 mmol) in dry tetrahydrofuran (35 mL) was added 1,1'-carbonyldiimidazole (0.89 g, 5.5 mmol). The mixture was heated to 45° C. in an ultrasound bath for 30 minutes, then 3-fluoro-4-phenylsulfonylbenzeneamine (1.35 g, 5.4 mmol) was added in one portion. The reaction mixture was heated at 65° C. in the ultrasound bath for 30 hours. Tetrahydrofuran was removed from the reaction mixture in vacuo, and the residue partitioned between water and ethyl ether. The aqueous layer was extracted with ethyl ether (2×50 mL), and the combined ether portions were dried (MgSO4 and concentrated in vacuo to an off-white solid. The solid was dissolved in ethyl ether, treated with HCl/ethyl ether and filtered to remove unreacted 3-fluoro-4-phenylsulfonylbenzeneamine. The filtrate was concentrated in vacuo, and the resulting solid recrystallized from ethyl ether/hexane to yield the title propanamide as a white solid (0.32 g, 13%); mp 188°-189° C. 1H--NMR (250 MHz, d6 --DMSO): 7.62-7.84 (m, 4H, aromatic) 7.91-7.94 (m, 3H, aromatic) 8.03-8.09 (m, 2H, aromatic) 9.60 (s, 1H, NH). MS (CI, CH4): 446 (M+1).

Workup

  1. temperatureThe reaction mixture was heated at 65° C. in the ultrasound bath for 30 hours
  2. customTetrahydrofuran was removed from the reaction mixture in vacuo
  3. customthe residue partitioned between water and ethyl ether
  4. extractionThe aqueous layer was extracted with ethyl ether (2×50 mL)
  5. dry with materialthe combined ether portions were dried (MgSO4
  6. concentrationconcentrated in vacuo to an off-white solid
  7. dissolutionThe solid was dissolved in ethyl ether
  8. additiontreated with HCl/ethyl ether
  9. filtrationfiltered
  10. customto remove unreacted 3-fluoro-4-phenylsulfonylbenzeneamine
  11. concentrationThe filtrate was concentrated in vacuo
  12. customthe resulting solid recrystallized from ethyl ether/hexane

Sources & evidence

ORD record
ord-80cf6ac5d8f9433fa3fb78ec12451518
Source dataset
uspto-grants-1993_12
Patent number
US05272163

Reaction notes

Loading…