Tetrahydrofuran → 4'-Trifluoromethyl-biphenyl-2-carboxylic acid (3-amino-phenyl)-amide

HRID 841838Notes

Reaction equation

HRID 841838 reaction equation
C([O-])=O.[NH4+].[N+:5]([C:8]1[CH:9]=[C:10]([NH:14][C:15]([C:17]2[C:18]([C:23]3[CH:28]=[CH:27][C:26]([C:29]([F:32])([F:31])[F:30])=[CH:25][CH:24]=3)=[CH:19][CH:20]=[CH:21][CH:22]=2)=[O:16])[CH:11]=[CH:12][CH:13]=1)([O-])=O.C1COCC1>[OH-].[OH-].[Pd+2].C(O)(C)C.C(OCC)(=O)C>[NH2:5][C:8]1[CH:9]=[C:10]([NH:14][C:15]([C:17]2[C:18]([C:23]3[CH:28]=[CH:27][C:26]([C:29]([F:30])([F:31])[F:32])=[CH:25][CH:24]=3)=[CH:19][CH:20]=[CH:21][CH:22]=2)=[O:16])[CH:11]=[CH:12][CH:13]=1

Participants

7

Reactant 3

HCID 8028TetrahydrofuranHCID 2723923Ammonium formateHCID 101569574'-Trifluoromethyl-biphenyl-2-carboxylic acid (3-nitro-phenyl)-amide

Product 1

HCID 99248284'-Trifluoromethyl-biphenyl-2-carboxylic acid (3-amino-phenyl)-amideYield 94%

Reagents, catalysts & solvents 3

HCID 9942167Palladium hydroxideCatalystHCID 3776IsopropanolSolventHCID 8857Ethyl AcetateSolvent

Procedure

Ammonium formate (16.3 g, 258 mmol, 3 equiv), followed by Pearlman's catalyst [Pd(OH)2] (6.03 g, 4.30 mmol, 0.05 equiv) was added to a solution of 4′-trifluoromethyl-biphenyl-2-carboxylic acid (3-nitro-phenyl)-amide (33.2 g, 85.9 mmol, 1 equiv) in isopropanol (330 mL, 10 volumes) and ethyl acetate (170 mL, 5 volumes). The mixture was heated at reflux for 3 hours. After cooling, THF (500 mL) was added to the reaction mixture to help solubilize the product. The reaction mixture was filtered through diatomaceous earth and the filtrate was concentrated to about 100 mL. Ethyl acetate (600 mL) and THF (200 mL) were added. The organic layer was washed with saturated sodium bicarbonate solution (300 mL), dried over sodium sulfate, filtered, and concentrated to afford 4′-trifluoromethyl-biphenyl-2-carboxylic acid (3-amino-phenyl)-amide (28.7 g, 94%) as an off-white solid.

Workup

  1. temperatureThe mixture was heated
  2. temperatureat reflux for 3 hours
  3. temperatureAfter cooling
  4. filtrationThe reaction mixture was filtered through diatomaceous earth
  5. concentrationthe filtrate was concentrated to about 100 mL
  6. additionEthyl acetate (600 mL) and THF (200 mL) were added
  7. washThe organic layer was washed with saturated sodium bicarbonate solution (300 mL)
  8. dry with materialdried over sodium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated

Sources & evidence

ORD record
ord-7a7527c6641c4d2699f631b6696b603a
Source dataset
uspto-grants-2002_04
Patent number
US06369075B1

Reaction notes

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