Dimethylformamide → 3-(3-Fluorophenyl)-N-(3-hydroxy-2,6-dimethyl-phenyl)-5-methoxy-benzamide

HRID 1771811Notes

Reaction equation

HRID 1771811 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)(C(Cl)=O)=O.CN(C=O)C.[NH2:30][C:31]1[C:32]([CH3:39])=[C:33]([OH:38])[CH:34]=[CH:35][C:36]=1[CH3:37]>C(Cl)Cl.C1COCC1.O>[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]([NH:30][C:31]2[C:36]([CH3:37])=[CH:35][CH:34]=[C:33]([OH:38])[C:32]=2[CH3:39])=[O:13])[CH:5]=[CH:6][CH:7]=1

Participants

8

Reactant 4

HCID 6228DimethylformamideHCID 65578Oxalyl chlorideHCID 141306083-Amino-2,4-dimethylphenolHCID 463129223-(3-Fluorophenyl)-5-methoxybenzoic acid

Product 1

HCID 894437283-(3-Fluorophenyl)-N-(3-hydroxy-2,6-dimethyl-phenyl)-5-methoxy-benzamideYield 57.6%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of 3-(3-fluorophenyl)-5-methoxy-benzoic acid (intermediate III(i)) (1.4 g, 5.7 mmol, 1.0 eq) in CH2Cl2 (15 mL) were added (COCl)2 (2.2 g, 17.3 mmol, 3.0 eq) and DMF (0.01 mL). The reaction mixture was stirred at room temperature for 1.5 h then the solvent and excess reagent removed under reduced pressure. The residue obtained was dissolved in THF (20 mL) and added dropwise to a solution of 3-amino-2,4-dimethylphenol (intermediate X(c)) (791 mg, 5.77 mmol, 1.0 eq) in THF (20 mL) at 0° C. The solution was allowed to warm to room temperature and stirred for 1 h. The reaction 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 residue obtained was purified by column chromatography (petroleum ether: EtOAc, 100:1 to 1:1) to give the title compound as a white solid (1.2 g, 57%).

Workup

  1. customthe solvent and excess reagent removed under reduced pressure
  2. customThe residue obtained
  3. temperatureto warm to room temperature
  4. stirringstirred for 1 h
  5. extractionextracted with EtOAc
  6. washThe combined organic extracts were washed with water and brine
  7. dry with materialdried (Na2SO4)
  8. filtrationfiltered
  9. customevaporated in vacuo
  10. customThe residue obtained
  11. customwas purified by column chromatography (petroleum ether: EtOAc, 100:1 to 1:1)

Sources & evidence

ORD record
ord-9e517559f36648c6af94ed04d5b838da
Source dataset
uspto-grants-2016_02
Patent number
US09249085B2

Reaction notes

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