Triethylamine → 5-bromo-N-(3,5-difluorophenyl)nicotinamide

HRID 1685524Notes

Reaction equation

HRID 1685524 reaction equation
C(Cl)(=O)C(Cl)=O.[Br:7][C:8]1[CH:9]=[N:10][CH:11]=[C:12]([CH:16]=1)[C:13]([OH:15])=O.[F:17][C:18]1[CH:19]=[C:20]([CH:22]=[C:23]([F:25])[CH:24]=1)[NH2:21].C(N(CC)CC)C>C(Cl)Cl.C(O)(=O)C.CN(C=O)C>[Br:7][C:8]1[CH:9]=[N:10][CH:11]=[C:12]([CH:16]=1)[C:13]([NH:21][C:20]1[CH:19]=[C:18]([F:17])[CH:24]=[C:23]([F:25])[CH:22]=1)=[O:15]

Participants

8

Reactant 4

HCID 8471TriethylamineHCID 65578Oxalyl chlorideHCID 887075-Bromonicotinic acidHCID 965953,5-Difluoroaniline

Product 1

HCID 416011495-bromo-N-(3,5-difluorophenyl)nicotinamideYield 93%

Reagents, catalysts & solvents 3

HCID 176Acetic AcidSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

Oxalyl chloride (1.2 mL) and DMF (25 μL) were added to 5-bromonicotinic acid (1.0 g, 4.95 mmol) suspended in CH2Cl2 (30 mL). The resulting mixture was stirred at room temperature for 12 min. It was then concentrated to dryness and azeotroped with toluene. The residual was then dissolved in toluene (30 mL). 3,5-Difluoroaniline (1.0 g, 7.8 mmol) was added followed by triethylamine (1.1 mL, 7.5 mmol). The resulting suspension was stirred at room temperature for 10 min. The reaction mixture was taken in 5% acetic acid(aq) (300 mL) and extracted with ethyl acetate (2×200 mL). The combined organic extract was washed with 1.0 M Na2CO3(aq) (2×100 mL) and brine. The organic layers were combined, dried (Na2SO4) and concentrated to dryness to provide the title compound (1.4 g, 93%). MS (APCI) m/z 313, 315 (M+H)+.

Workup

  1. concentrationIt was then concentrated to dryness
  2. customazeotroped with toluene
  3. dissolutionThe residual was then dissolved in toluene (30 mL)
  4. stirringThe resulting suspension was stirred at room temperature for 10 min
  5. extractionextracted with ethyl acetate (2×200 mL)
  6. extractionThe combined organic extract
  7. washwas washed with 1.0 M Na2CO3(aq) (2×100 mL) and brine
  8. dry with materialdried (Na2SO4)
  9. concentrationconcentrated to dryness

Sources & evidence

ORD record
ord-f52c81fc79e24d85b3f93f6952166dde
Source dataset
uspto-grants-2012_04
Patent number
US08148408B2

Reaction notes

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