Water → N-(2,6-difluoro-3-hydroxy-phenyl)-3-(3-fluorophenyl)-5-methoxy-benzamide

HRID 1771672Notes

Reaction equation

HRID 1771672 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([C:8]2[CH:9]=[C:10]([CH:14]=[C:15]([O:17][CH3:18])[CH:16]=2)[C:11]([OH:13])=O)[CH:5]=[CH:6][CH:7]=1.C(Cl)(=O)C(Cl)=O.[NH2:25][C:26]1[C:27]([F:34])=[C:28]([OH:33])[CH:29]=[CH:30][C:31]=1[F:32].O>C(Cl)Cl.CN(C=O)C.C1COCC1>[F:34][C:27]1[C:28]([OH:33])=[CH:29][CH:30]=[C:31]([F:32])[C:26]=1[NH:25][C:11](=[O:13])[C:10]1[CH:14]=[C:15]([O:17][CH3:18])[CH:16]=[C:8]([C:4]2[CH:5]=[CH:6][CH:7]=[C:2]([F:1])[CH:3]=2)[CH:9]=1

Participants

8

Reactant 4

HCID 962WaterHCID 65578Oxalyl chlorideHCID 227559833-Amino-2,4-difluorophenolHCID 463129223-(3-Fluorophenyl)-5-methoxybenzoic acid

Product 1

HCID 89444129N-(2,6-difluoro-3-hydroxy-phenyl)-3-(3-fluorophenyl)-5-methoxy-benzamideYield 68%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideCatalystHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of 3-(3-fluorophenyl)-5-methoxy-benzoic acid (747 mg, 3.0 mmol, 1.1 eq) in DCM (20 mL) was added oxalyl chloride (1.05 g, 8.3 mmol, 3.0 eq) and DMF (3 drops). The reaction mixture was stirred at room temperature for 2 h, then concentrated. The oil obtained was dissolved in THF (5 mL) and added dropwise to a cooled solution of 3-Amino-2,4-difluoro-phenol (intermediate X(a)) (400 mg, 2.76 mmol, 1.0 eq) in THF (25 mL) at 0° C. After addition, the reaction mixture was stirred at room temperature for 2 h. The resulting mixture was poured into water and extracted with EtOAc. The organic extract was washed with water and brine, dried (Na2SO4), filtered, evaporated in vacuo and purified by column chromatography (EtOAc:petroleum ether, 0:1 to 1:3) to give the title compound as a yellow solid (700 mg, 68%).

Workup

  1. concentrationconcentrated
  2. customThe oil obtained
  3. additionAfter addition
  4. stirringthe reaction mixture was stirred at room temperature for 2 h
  5. extractionextracted with EtOAc
  6. extractionThe organic extract
  7. washwas washed with water and brine
  8. dry with materialdried (Na2SO4)
  9. filtrationfiltered
  10. customevaporated in vacuo
  11. custompurified by column chromatography (EtOAc:petroleum ether, 0:1 to 1:3)

Sources & evidence

ORD record
ord-fc935eb09fc340d3bde54337c8d7f523
Source dataset
uspto-grants-2016_02
Patent number
US09249085B2

Reaction notes

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