Sodium Carbonate → N-(2,6-difluoro-3-hydroxy-phenyl)-5-(3-fluorophenyl)-2,3-dimethyl-benzamide

HRID 1771703Notes

Reaction equation

HRID 1771703 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([C:8]2[CH:9]=[C:10]([CH3:18])[C:11]([CH3:17])=[C:12]([CH:16]=2)[C:13]([OH:15])=O)[CH:5]=[CH:6][CH:7]=1.C(Cl)(C(Cl)=O)=O.[NH2:25][C:26]1[C:27]([F:34])=[C:28]([OH:33])[CH:29]=[CH:30][C:31]=1[F:32].C([O-])([O-])=O.[Na+].[Na+]>C(Cl)Cl.C1COCC1.CCOC(C)=O.O.CN(C=O)C>[F:34][C:27]1[C:28]([OH:33])=[CH:29][CH:30]=[C:31]([F:32])[C:26]=1[NH:25][C:13](=[O:15])[C:12]1[CH:16]=[C:8]([C:4]2[CH:5]=[CH:6][CH:7]=[C:2]([F:1])[CH:3]=2)[CH:9]=[C:10]([CH3:18])[C:11]=1[CH3:17]

Participants

10

Reactant 4

HCID 10340Sodium CarbonateHCID 65578Oxalyl chlorideHCID 227559833-Amino-2,4-difluorophenolHCID 894435205-(3-Fluorophenyl)-2,3-dimethyl-benzoic acid

Product 1

HCID 89443837N-(2,6-difluoro-3-hydroxy-phenyl)-5-(3-fluorophenyl)-2,3-dimethyl-benzamideYield 15.7%

Reagents, catalysts & solvents 5

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 5-(3-fluorophenyl)-2,3-dimethyl-benzoic acid (3.82 g, 15.6 mmol, 5.8 eq) in DCM (30 mL) was added (COCl)2 (5.96 g, 46.8 mmol, 17.0 eq) and DMF (0.5 mL). The mixture was stirred at room temperature under N2 for 2 h then the solvent removed in vacuo. The residue obtained was dissolved in THF (10 mL) and added to a mixture of 3-amino-2,4-difluoro-phenol (intermediate X(a)) (0.4 g, 2.75 mmol, 1.0 eq) and Na2CO3 (0.87 g, 8.26 mmol, 3.0 eq) in THF. The reaction was stirred at room temperature overnight then water and EtOAc were added. The organic extract was washed with water, dried (Na2SO4), filtered and evaporated in vacuo. The residue obtained was purified by column chromatography (DCM:MeOH, 0:1 to 1:50) to give the title compound as a solid (0.16 g, 15%).

Workup

  1. customthe solvent removed in vacuo
  2. customThe residue obtained
  3. stirringThe reaction was stirred at room temperature overnight
  4. extractionThe organic extract
  5. washwas washed with water
  6. dry with materialdried (Na2SO4)
  7. filtrationfiltered
  8. customevaporated in vacuo
  9. customThe residue obtained
  10. customwas purified by column chromatography (DCM:MeOH, 0:1 to 1:50)

Sources & evidence

ORD record
ord-a528e0cb9a0944e5babf0e96d91e3ea1
Source dataset
uspto-grants-2016_02
Patent number
US09249085B2

Reaction notes

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