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

HRID 1771829Notes

Reaction equation

HRID 1771829 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)(=O)C(Cl)=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.[Na+].[Na+]>C(Cl)Cl.C1COCC1.CN(C=O)C>[F:32][C:31]1[C:26]([NH:25][C:13](=[O:15])[C:12]2[CH:16]=[C:8]([C:4]3[CH:5]=[CH:6][CH:7]=[C:2]([F:1])[CH:3]=3)[CH:9]=[C:10]([CH3:18])[C:11]=2[CH3:17])=[C:27]([CH3:34])[C:28]([OH:33])=[CH:29][CH:30]=1

Participants

8

Reactant 4

HCID 10340Sodium CarbonateHCID 65578Oxalyl chlorideHCID 177757273-Amino-4-fluoro-2-methylphenolHCID 894435205-(3-Fluorophenyl)-2,3-dimethyl-benzoic acid

Product 1

HCID 89443835N-(6-Fluoro-3-hydroxy-2-methyl-phenyl)-5-(3-fluorophenyl)-2,3-dimethyl-benzamideYield 40.8%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of 5-(3-fluorophenyl)-2,3-dimethyl-benzoic acid (intermediate III(m)) (500 mg, 2.0 mmol, 1.0 eq) in CH2Cl2 (10 mL) at 0° C. was added oxalyl chloride (770 mg, 6.1 mmol, 3.0 eq) and DMF (0.1 mL) and the reaction was stirred for 1 h. The solvent and excess reagent were removed under reduced pressure and the residue obtained was dissolved in THF (10 mL) and added to a mixture of 3-amino-4-fluoro-2-methyl-phenol (intermediate X(e)) (280 mg, 2.0 mmol, 1.0 eq) and Na2CO3 (860 mg, 8.1 mmol, 4.0 eq) in THF (10 mL) at 0° C. The reaction was stirred for 3 h, then filtered and concentrated in vacuo. The residue obtained was purified by column chromatography (petroleum ether:EtOAc, 400:1 to 4:3) to give the title compound as a brown solid (300 mg, 40%).

Workup

  1. customThe solvent and excess reagent were removed under reduced pressure
  2. customthe residue obtained
  3. stirringThe reaction was stirred for 3 h
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe residue obtained
  7. customwas purified by column chromatography (petroleum ether:EtOAc, 400:1 to 4:3)

Sources & evidence

ORD record
ord-43e09408dc6c415aa96d918092778732
Source dataset
uspto-grants-2016_02
Patent number
US09249085B2

Reaction notes

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