Hydrochloric Acid → 2-Fluoro-5-(3-fluorophenyl)-N-(3-hydroxy-2,6-dimethyl-phenyl)benzamide

HRID 1771637Notes

Reaction equation

HRID 1771637 reaction equation
[F:1][C:2]1[CH:10]=[CH:9][C:8]([C:11]2[CH:16]=[CH:15][CH:14]=[C:13]([F:17])[CH:12]=2)=[CH:7][C:3]=1[C:4]([OH:6])=O.C(Cl)(=O)C(Cl)=O.[NH2:24][C:25]1[C:26]([CH3:33])=[C:27]([OH:32])[CH:28]=[CH:29][C:30]=1[CH3:31].C([O-])(O)=O.[Na+].Cl>C(Cl)Cl.C1COCC1.CN(C=O)C>[F:1][C:2]1[CH:10]=[CH:9][C:8]([C:11]2[CH:16]=[CH:15][CH:14]=[C:13]([F:17])[CH:12]=2)=[CH:7][C:3]=1[C:4]([NH:24][C:25]1[C:30]([CH3:31])=[CH:29][CH:28]=[C:27]([OH:32])[C:26]=1[CH3:33])=[O:6]

Participants

9

Reactant 5

HCID 313Hydrochloric AcidHCID 65578Oxalyl chlorideHCID 516892Sodium BicarbonateHCID 141306083-Amino-2,4-dimethylphenolHCID 463123323',4-Difluoro-[1,1'-biphenyl]-3-carboxylic acid

Product 1

HCID 894453412-Fluoro-5-(3-fluorophenyl)-N-(3-hydroxy-2,6-dimethyl-phenyl)benzamideYield 42%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

To a mixture of 2-fluoro-5-(3-fluorophenyl)benzoic acid (intermediate III(a)) (632 mg, 2.7 mmol, 1.0 eq) and oxalyl chloride (1.03 g, 8.1 mmol, 3.0 eq) in DCM (30 mL) was added DMF (0.3 mL). The reaction mixture was stirred at room temperature for 1 h. The resulting mixture was concentrated to remove the solvent and excess oxalyl chloride then the residue obtained was dissolved in THF (20 mL). This solution was added dropwise to a suspension of 3-amino-2,4-dimethyl-phenol (370 mg, 2.7 mmol, 1.0 eq) and NaHCO3 (680 mg, 8.1 mmol, 3.0 eq) in THF (20 mL). After addition was complete, the reaction mixture was stirred at room temperature for 30 min. The resulting mixture was adjusted to pH 3 by addition of 1M HCl and the aqueous layer extracted with EtOAc. The organic extract was dried (Na2SO4), filtered, evaporated in vacuo and purified by column chromatography (EtOAc:petroleum ether, 0:1 to 1:1) to give the title compound as a yellow solid (400 mg, 42%).

Workup

  1. concentrationThe resulting mixture was concentrated
  2. customto remove the solvent and excess oxalyl chloride
  3. customthe residue obtained
  4. additionAfter addition
  5. stirringthe reaction mixture was stirred at room temperature for 30 min
  6. extractionthe aqueous layer extracted with EtOAc
  7. extractionThe organic extract
  8. dry with materialwas dried (Na2SO4)
  9. filtrationfiltered
  10. customevaporated in vacuo
  11. custompurified by column chromatography (EtOAc:petroleum ether, 0:1 to 1:1)

Sources & evidence

ORD record
ord-f8d32dc5eac7416eae34a048168b0a41
Source dataset
uspto-grants-2016_02
Patent number
US09249085B2

Reaction notes

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