Diethylamine → 5-bromo-2-(6-chloropyridin-3-yloxy)-N,N-diethyl-4-fluorobenzamide

HRID 335896Notes

Reaction equation

HRID 335896 reaction equation
[Br:1][C:2]1[C:3]([F:19])=[CH:4][C:5]([O:11][C:12]2[CH:13]=[N:14][C:15]([Cl:18])=[CH:16][CH:17]=2)=[C:6]([CH:10]=1)[C:7]([OH:9])=O.[CH2:20]([NH:22][CH2:23][CH3:24])[CH3:21]>CN(C=O)C>[Br:1][C:2]1[C:3]([F:19])=[CH:4][C:5]([O:11][C:12]2[CH:13]=[N:14][C:15]([Cl:18])=[CH:16][CH:17]=2)=[C:6]([CH:10]=1)[C:7]([N:22]([CH2:23][CH3:24])[CH2:20][CH3:21])=[O:9]

Participants

4

Reactant 2

HCID 8021DiethylamineHCID 866584825-Bromo-2-(6-chloropyridin-3-yloxy)-4-fluorobenzoic acid

Product 1

HCID 866584835-bromo-2-(6-chloropyridin-3-yloxy)-N,N-diethyl-4-fluorobenzamide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

(N,N,N′,N′-Tetramethyl-o-(1h-benzotriazol-1-yl)uronium tetrafluoroborate (6.95 g, 21.64 mmol) was added to a solution of 5-bromo-2-(6-chloropyridin-3-yloxy)-4-fluorobenzoic acid (5.00 g, 14.43 mmol) and diethylamine (8.00 mL, 77 mmol) in DMF (70 mL) at 0° C. The reaction was stirred 1.5 hours before being quenched with saturated sodium bicarbonate (100 mL). The reaction mixture was diluted with water (50 mL) and extracted with EtOAc (3×50 mL). The combined organic extracts were washed with saturated aqueous ammonium chloride, water, 10% aqueous sodium carbonate, saturated aqueous sodium chloride, and dried over sodium sulfate. The solution was filtered and concentrated in vacuo to provide a residue that was purified by silica gel chromatography (1:2 EtOAc in hexane) to provide 5-bromo-2-(6-chloropyridin-3-yloxy)-N,N-diethyl-4-fluorobenzamide. MS m/z=403.0 [M+H].

Workup

  1. custombefore being quenched with saturated sodium bicarbonate (100 mL)
  2. additionThe reaction mixture was diluted with water (50 mL)
  3. extractionextracted with EtOAc (3×50 mL)
  4. washThe combined organic extracts were washed with saturated aqueous ammonium chloride, water, 10% aqueous sodium carbonate, saturated aqueous sodium chloride
  5. dry with materialdried over sodium sulfate
  6. filtrationThe solution was filtered
  7. concentrationconcentrated in vacuo
  8. customto provide a residue that
  9. customwas purified by silica gel chromatography (1:2 EtOAc in hexane)

Sources & evidence

ORD record
ord-f87e78501742425985bf55a501337c36
Source dataset
uspto-grants-2014_11
Patent number
US08883782B2

Reaction notes

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