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

HRID 1771788Notes

Reaction equation

HRID 1771788 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([C:8]2[CH:9]=[C:10]([CH:14]=[C:15]([CH3:17])[CH:16]=2)[C:11]([OH:13])=O)[CH:5]=[CH:6][CH:7]=1.C(Cl)(C(Cl)=O)=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+]>C(Cl)Cl.CN(C=O)C.C1COCC1.O>[F:1][C:2]1[CH:3]=[C:4]([C:8]2[CH:9]=[C:10]([CH:14]=[C:15]([CH3:17])[CH:16]=2)[C:11]([NH:24][C:25]2[C:30]([CH3:31])=[CH:29][CH:28]=[C:27]([OH:32])[C:26]=2[CH3:33])=[O:13])[CH:5]=[CH:6][CH:7]=1

Participants

9

Reactant 4

HCID 65578Oxalyl chlorideHCID 516892Sodium BicarbonateHCID 141306083-Amino-2,4-dimethylphenolHCID 463145783-(3-Fluorophenyl)-5-methyl-benzoic acid

Product 1

HCID 894437033-(3-Fluorophenyl)-N-(3-hydroxy-2,6-dimethyl-phenyl)-5-methyl-benzamideYield 70.3%

Reagents, catalysts & solvents 4

HCID 6228DimethylformamideCatalystHCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of 3-(3-fluorophenyl)-5-methyl-benzoic acid (300 mg, 1.30 mmol, 1.1 eq) (III(q)) in CH2Cl2 (10 mL) was added (COCl)2 (610 mg, 4.81 mmol, 3.3 eq) and DMF (5 drops). The reaction mixture was stirred at room temperature for 2 h. The resulting mixture was concentrated under reduced pressure to remove the solvent and excess reagent. The residue obtained was dissolved in THF (10 mL) and added dropwise to a mixture of 3-amino-2,4-dimethylphenol (intermediate X(c)) (163 mg, 1.18 mmol, 1.0 eq) and NaHCO3 (612 mg, 7.30 mmol, 5.0 eq) in THF (20 mL) at 0° C. After addition was completed, the reaction mixture was allowed to warm to room temperature and stirred for 1 h. The resulting mixture was poured into water and extracted with EtOAc. The combined organic extracts were washed with water and brine, dried (Na2SO4), filtered, and evaporated in vacuo. The crude product obtained was purified by column chromatography (CH2Cl2: MeOH, 500:1 to 300:1) to give the title compound as a white solid (290 mg, 57%).

Workup

  1. concentrationThe resulting mixture was concentrated under reduced pressure
  2. customto remove the solvent and excess reagent
  3. customThe residue obtained
  4. additionAfter addition
  5. temperatureto warm to room temperature
  6. stirringstirred for 1 h
  7. extractionextracted with EtOAc
  8. washThe combined organic extracts were washed with water and brine
  9. dry with materialdried (Na2SO4)
  10. filtrationfiltered
  11. customevaporated in vacuo
  12. customThe crude product obtained
  13. customwas purified by column chromatography (CH2Cl2: MeOH, 500:1 to 300:1)

Sources & evidence

ORD record
ord-2af70e319fdc4809800b807611752005
Source dataset
uspto-grants-2016_02
Patent number
US09249085B2

Reaction notes

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