Potassium Carbonate → N-(6-Fluoro-3-hydroxy-2-methyl-phenyl)-3-(3-fluorophenyl)-5-methoxy-benzamide

HRID 1771765Notes

Reaction equation

HRID 1771765 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.[NH2:25][C:26]1[C:27]([CH3:34])=[C:28]([OH:33])[CH:29]=[CH:30][C:31]=1[F:32].C([O-])([O-])=O.[K+].[K+]>C(Cl)Cl.C1COCC1.O.CN(C=O)C>[F:32][C:31]1[C:26]([NH:25][C:11](=[O:13])[C:10]2[CH:14]=[C:15]([O:17][CH3:18])[CH:16]=[C:8]([C:4]3[CH:5]=[CH:6][CH:7]=[C:2]([F:1])[CH:3]=3)[CH:9]=2)=[C:27]([CH3:34])[C:28]([OH:33])=[CH:29][CH:30]=1

Participants

9

Reactant 4

HCID 11430Potassium CarbonateHCID 65578Oxalyl chlorideHCID 177757273-Amino-4-fluoro-2-methylphenolHCID 463129223-(3-Fluorophenyl)-5-methoxybenzoic acid

Product 1

HCID 89443585N-(6-Fluoro-3-hydroxy-2-methyl-phenyl)-3-(3-fluorophenyl)-5-methoxy-benzamideYield 64.5%

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of 3-(3-fluorophenyl)-5-methoxy-benzoic acid (524 mg, 2.1 mmol, 1.0 eq) in CH2Cl2 (10 mL) was added dropwise (COCl)2 (810 mg, 6.4 mmol, 3 eq) at 0° C. DMF (0.1 mL) was added and the reaction mixture stirred at room temperature for 3 h. The solvent was removed under reduced pressure and the residue obtained was dissolved in THF (20 mL) and added dropwise to a mixture of 3-amino-4-fluoro-2-methyl-phenol (300 mg, 2.1 mmol, 1 eq) and K2CO3 (1.47 g, 10.6 mmol, 5 eq.) in THF (20 mL) at 0° C. After the addition, the reaction mixture was stirred at room temperature for 3 h. The resulting mixture was poured into water and extracted with EtOAc. The organic extract was washed with brine, dried (Na2SO4), filtered and evaporated in vacuo. The residue obtained was purified by column chromatography (petroleum ether:EtOAc, 20:1) to give the title compound as yellow solid (500 mg, 63%).

Workup

  1. customThe solvent was removed under reduced pressure
  2. customthe residue obtained
  3. additionAfter the addition
  4. stirringthe reaction mixture was stirred at room temperature for 3 h
  5. extractionextracted with EtOAc
  6. extractionThe organic extract
  7. washwas washed with brine
  8. dry with materialdried (Na2SO4)
  9. filtrationfiltered
  10. customevaporated in vacuo
  11. customThe residue obtained
  12. customwas purified by column chromatography (petroleum ether:EtOAc, 20:1)

Sources & evidence

ORD record
ord-def31121ee104dac8c3bcdf3cf14abbc
Source dataset
uspto-grants-2016_02
Patent number
US09249085B2

Reaction notes

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