Oxalyl chloride → N-(2,6-Difluoro-3-hydroxy-phenyl)-2, 3-dimethyl-5-phenyl-benzamide

HRID 1771834Notes

Reaction equation

HRID 1771834 reaction equation
[CH3:1][C:2]1[C:10]([CH3:11])=[CH:9][C:8]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)=[CH:7][C:3]=1[C:4]([OH:6])=O.C(Cl)(=O)C(Cl)=O.[NH2:24][C:25]1[C:26]([F:33])=[C:27]([OH:32])[CH:28]=[CH:29][C:30]=1[F:31].C([O-])(O)=O.[Na+]>C(Cl)Cl.C1COCC1.O>[F:33][C:26]1[C:27]([OH:32])=[CH:28][CH:29]=[C:30]([F:31])[C:25]=1[NH:24][C:4](=[O:6])[C:3]1[CH:7]=[C:8]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[CH:9]=[C:10]([CH3:11])[C:2]=1[CH3:1]

Participants

8

Reactant 4

HCID 65578Oxalyl chlorideHCID 516892Sodium BicarbonateHCID 227559833-Amino-2,4-difluorophenolHCID 894441102,3-Dimethyl-5-phenyl-benzoic acid

Product 1

HCID 89443618N-(2,6-Difluoro-3-hydroxy-phenyl)-2, 3-dimethyl-5-phenyl-benzamideYield 49%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 2,3-dimethyl-5-phenyl-benzoic acid (315 mg, 1.4 mmol, 1.1 eq) in CH2Cl2 (10 mL) was added oxalyl chloride (530 mg, 4.2 mmol, 3.3 eq) at 0° C. The reaction was allowed to warm to room temperature and stirred for 1 h. The solvent and excess reagent were removed under reduced pressure and the residue that remained dissolved in THF (10 mL) and added dropwise to a mixture of 3-amino-2,4-difluoro-phenol (intermediate X(a)) (184 mg, 1.3 mmol, 1.0 eq) and NaHCO3 (532 mg, 6.3 mmol, 5.0 eq) in THF (8 mL) at 0° C. The reaction was stirred at room temperature for 2 h, water was added and the aqueous layer was extracted with EtOAc. The combined organic extracts were washed with water and brine, dried (Na2SO4), filtered, and evaporated in vacuo. The residue was purified by column chromatography (petroleum ether:EtOAc, 20:1 to 10:1, then CH2Cl2:MeOH, 500:1 to 100:1) to give the title compound as a yellow solid (220 mg, 49%).

Workup

  1. customThe solvent and excess reagent were removed under reduced pressure
  2. dissolutionthe residue that remained dissolved in THF (10 mL)
  3. stirringThe reaction was stirred at room temperature for 2 h
  4. extractionthe aqueous layer was extracted with EtOAc
  5. washThe combined organic extracts were washed with water and brine
  6. dry with materialdried (Na2SO4)
  7. filtrationfiltered
  8. customevaporated in vacuo
  9. customThe residue was purified by column chromatography (petroleum ether

Sources & evidence

ORD record
ord-4d814c142c5b4b698222a32fe3be6db5
Source dataset
uspto-grants-2016_02
Patent number
US09249085B2

Reaction notes

Loading…