4'-Trifluoromethyl-biphenyl-2-carboxylic acid (3-amino-phenyl)-amide → 4'-Trifluoromethyl-biphenyl-2-carboxylic acid (3-formyl-quinolin-7-yl)-amide

HRID 51976Notes

Reaction equation

HRID 51976 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]([NH:8][C:9]([C:11]2[C:12]([C:17]3[CH:22]=[CH:21][C:20]([C:23]([F:26])([F:25])[F:24])=[CH:19][CH:18]=3)=[CH:13][CH:14]=[CH:15][CH:16]=2)=[O:10])[CH:5]=[CH:6][CH:7]=1>C(O)C>[CH:9]([C:11]1[CH:16]=[N:1][C:2]2[C:7]([CH:12]=1)=[CH:6][CH:5]=[C:4]([NH:8][C:9]([C:11]1[C:12]([C:17]3[CH:22]=[CH:21][C:20]([C:23]([F:24])([F:25])[F:26])=[CH:19][CH:18]=3)=[CH:13][CH:14]=[CH:15][CH:16]=1)=[O:10])[CH:3]=2)=[O:10]

Participants

3

Reactant 1

HCID 99248284'-Trifluoromethyl-biphenyl-2-carboxylic acid (3-amino-phenyl)-amide

Product 1

HCID 102022794'-Trifluoromethyl-biphenyl-2-carboxylic acid (3-formyl-quinolin-7-yl)-amideYield 200%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

A slurry of 4′-trifluoromethyl-biphenyl-2-carboxylic acid (3-amino-phenyl)-amide (6.5 g, 18.2 mmol, 1 equiv) and 2-dimethylaminomethylene-1,3-bis(dimethylimmonio)propane bis(tetrafluoroborate) (19.5 g, 54.7 mmol, 3 equiv) in ethanol (200 mL, 30 volumes) was heated at reflux for 24 hours. The reaction became homogeneous after heating for 4 hours. The solution was concentrated and the residue was dissolved in THF (100 mL, 15 volumes) and 1 N HCl (100 mL, 15 volumes). The reaction mixture was stirred at room temperature for 3 hours, then poured into a saturated solution of sodium bicarbonate (100 mL), and extracted with ethyl acetate (2×100 mL). The combined organic layers were dried over sodium sulfate, treated with activated charcoal, filtered, (6.5 g, 1 weight equiv) and concentrated to afford 4′-trifluoromethyl-biphenyl-2-carboxylic acid (3-formyl-quinolin-7-yl)-amide (7.65 g, 100% crude yield) as a yellow foam. The crude product was clean by 1H NMR and used in the next step without further purification.

Workup

  1. temperatureat reflux for 24 hours
  2. temperatureafter heating for 4 hours
  3. concentrationThe solution was concentrated
  4. dissolutionthe residue was dissolved in THF (100 mL, 15 volumes)
  5. additionpoured into a saturated solution of sodium bicarbonate (100 mL)
  6. extractionextracted with ethyl acetate (2×100 mL)
  7. dry with materialThe combined organic layers were dried over sodium sulfate
  8. additiontreated with activated charcoal
  9. filtrationfiltered
  10. concentration(6.5 g, 1 weight equiv) and concentrated

Sources & evidence

ORD record
ord-fcbe5bd92cc14a9dacef20768162feb9
Source dataset
uspto-grants-2004_03
Patent number
US06713489B2

Reaction notes

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