Water → 2-Fluoro-N-(6-fluoro-3-hydroxy-2-methyl-phenyl)-5-(3-fluorophenyl)benzamide

HRID 1771654Notes

Reaction equation

HRID 1771654 reaction equation
[F:1][C:2]1[CH:10]=[CH:9][C:8]([C:11]2[CH:16]=[CH:15][CH:14]=[C:13]([F:17])[CH:12]=2)=[CH:7][C:3]=1[C:4]([OH:6])=O.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[F:31].O>C(Cl)Cl.CN(C=O)C.C1COCC1>[F:1][C:2]1[CH:10]=[CH:9][C:8]([C:11]2[CH:16]=[CH:15][CH:14]=[C:13]([F:17])[CH:12]=2)=[CH:7][C:3]=1[C:4]([NH:24][C:25]1[C:30]([F:31])=[CH:29][CH:28]=[C:27]([OH:32])[C:26]=1[CH3:33])=[O:6]

Participants

8

Reactant 4

HCID 962WaterHCID 65578Oxalyl chlorideHCID 177757273-Amino-4-fluoro-2-methylphenolHCID 463123323',4-Difluoro-[1,1'-biphenyl]-3-carboxylic acid

Product 1

HCID 894442512-Fluoro-N-(6-fluoro-3-hydroxy-2-methyl-phenyl)-5-(3-fluorophenyl)benzamideYield 59.1%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideCatalystHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

To a mixture of 2-fluoro-5-(3-fluorophenyl)benzoic acid (intermediate III(a)) (365 mg, 1.56 mmol, 1.1 eq) and (COCl)2 (541 mg, 4.26 mmol, 3.0 eq) in DCM (10 mL) was added DMF (3 drops). The reaction mixture was stirred at room temperature for 2 h, then concentrated in vacuo. The residue obtained was dissolved in THF (5 mL) and added dropwise to a solution of 3-amino-4-fluoro-2-methyl-phenol (200 mg, 1.42 mmol, 1.0 eq) in THF (15 mL) at 0° C. After the addition was completed, the reaction mixture was allowed to warm to room temperature and stirred for 2 h. The resulting mixture was poured into water and extracted with EtOAc. The organic extract was washed with water and brine, dried (Na2SO4), filtered, evaporated in vacuo and purified by column chromatography (EtOAc:petroleum ether, 0:1 to 1:3) to give the title compound as a yellow solid (300 mg, 59%).

Workup

  1. concentrationconcentrated in vacuo
  2. customThe residue obtained
  3. additionAfter the addition
  4. temperatureto warm to room temperature
  5. stirringstirred for 2 h
  6. extractionextracted with EtOAc
  7. extractionThe organic extract
  8. washwas washed with water and brine
  9. dry with materialdried (Na2SO4)
  10. filtrationfiltered
  11. customevaporated in vacuo
  12. custompurified by column chromatography (EtOAc:petroleum ether, 0:1 to 1:3)

Sources & evidence

ORD record
ord-c650287e00a54d5d8a05b6cab90c1bfa
Source dataset
uspto-grants-2016_02
Patent number
US09249085B2

Reaction notes

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