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

HRID 1771761ノート

反応式

HRID 1771761 の反応式
[F:1][C:2]1[C:10]([CH3:11])=[CH:9][C:8]([C:12]2[CH:17]=[CH:16][CH:15]=[C:14]([F:18])[CH:13]=2)=[CH:7][C:3]=1[C:4]([OH:6])=O.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[CH3:32].C([O-])(O)=O.[Na+]>C(Cl)Cl.CN(C=O)C.C1COCC1.O>[F:1][C:2]1[C:10]([CH3:11])=[CH:9][C:8]([C:12]2[CH:17]=[CH:16][CH:15]=[C:14]([F:18])[CH:13]=2)=[CH:7][C:3]=1[C:4]([NH:25][C:26]1[C:31]([CH3:32])=[CH:30][CH:29]=[C:28]([OH:33])[C:27]=1[CH3:34])=[O:6]

参加物

9

反応物 4

HCID 65578Oxalyl chlorideHCID 516892Sodium BicarbonateHCID 141306083-Amino-2,4-dimethylphenolHCID 894436582-Fluoro-5-(3-fluorophenyl)-3-methyl-benzoic acid

生成物 1

HCID 894443422-Fluoro-5-(3-fluorophenyl)-N-(3-hydroxy-2,6-dimethyl-phenyl)-3-methyl-benzamide収率 34%

試薬・触媒・溶媒 4

HCID 6228Dimethylformamide触媒HCID 962Water溶媒HCID 6344Dichloromethane溶媒HCID 8028Tetrahydrofuran溶媒2 回

実験手順

To a solution of 2-fluoro-5-(3-fluorophenyl)-3-methyl-benzoic acid (intermediate III(f)) (597 mg, 2.41 mmol, 1.1 eq) in CH2Cl2 (15 mL) and DMF (5 drops) was added (COCl)2 (916 mg, 7.22 mmol, 3.3 eq) at 0° C. The reaction mixture was stirred at room temperature for 1.5 h. The resulting mixture was concentrated under reduced pressure to remove the solvent and excess reagent and the residue obtained dissolved in THF (20 mL) and added dropwise to a solution of 3-amino-2,4-dimethylphenol (intermediate X(c)) (300 mg, 2.18 mmol, 1.0 eq) and NaHCO3 (920 mg, 10.9 mmol, 5 eq) in THF (20 mL) at 0° C. After the addition was completed, the reaction mixture was stirred at room temperature for 1 h. Water was added and the aqueous layer extracted with EtOAc. The organic extract was washed with water and brine, dried (Na2SO4), filtered, and evaporated in vacuo. The residue was purified by column chromatography (CH2Cl2:MeOH, 500:1 to 300:1) to give the title compound as a white solid (270 mg, 34%).

後処理

  1. concentrationThe resulting mixture was concentrated under reduced pressure
  2. customto remove the solvent and excess reagent
  3. customthe residue obtained
  4. additionAfter the addition
  5. stirringthe reaction mixture was stirred at room temperature for 1 h
  6. extractionthe aqueous layer extracted 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. customThe residue was purified by column chromatography (CH2Cl2:MeOH, 500:1 to 300:1)

出典と根拠

ORDレコード
ord-c2d3db5c991f44b790956f8ad225e1c9
出典データセット
uspto-grants-2016_02
特許番号
US09249085B2

反応ノート

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