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

HRID 1771796ノート

反応式

HRID 1771796 の反応式
[F:1][C:2]1[CH:3]=[C:4]([C:8]2[CH:9]=[C:10]([CH3:19])[C:11]([O:17][CH3:18])=[C:12]([CH:16]=2)[C:13]([OH:15])=O)[CH:5]=[CH:6][CH:7]=1.C(Cl)(C(Cl)=O)=O.[NH2:26][C:27]1[C:28]([CH3:35])=[C:29]([OH:34])[CH:30]=[CH:31][C:32]=1[CH3:33].C([O-])(O)=O.[Na+]>C(Cl)Cl.CN(C=O)C.C1COCC1.O>[F:1][C:2]1[CH:3]=[C:4]([C:8]2[CH:9]=[C:10]([CH3:19])[C:11]([O:17][CH3:18])=[C:12]([CH:16]=2)[C:13]([NH:26][C:27]2[C:32]([CH3:33])=[CH:31][CH:30]=[C:29]([OH:34])[C:28]=2[CH3:35])=[O:15])[CH:5]=[CH:6][CH:7]=1

参加物

9

反応物 4

HCID 65578Oxalyl chlorideHCID 516892Sodium BicarbonateHCID 141306083-Amino-2,4-dimethylphenolHCID 894437175-(3-Fluorophenyl)-2-methoxy-3-methyl-benzoic acid

生成物 1

HCID 894435135-(3-Fluorophenyl)-N-(3-hydroxy-2,6-dimethyl-phenyl)-2-methoxy-3-methyl-benzamide収率 82.1%

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 5-(3-fluorophenyl)-2-methoxy-3-methyl-benzoic acid (intermediate III(k)) (400 mg, 1.5 mmol, 1.1 eq) in CH2Cl2 (8 mL) was added (COCl)2 (585 mg, 4.6 mmol, 3.3 eq) and DMF (3 drops). The reaction mixture was stirred at room temperature for 1 h. The resulting mixture was concentrated under reduced pressure to remove the solvent and excess reagent and the residue obtained was dissolved in THF (8 mL) and added dropwise to a solution of 3-amino-2,4-dimethylphenol (intermediate X(c)) (192 mg, 1.4 mmol, 1.0 eq) and NaHCO3 (587 mg, 7.0 mmol, 5.0 eq) in THF (6 mL) at 0° C. After the addition was complete the reaction mixture was allowed to warm to room temperature and was stirred for 2 h. The resulting mixture was poured into water and extracted with EtOAc. The combined organic extracts were washed with water and brine, dried (Na2SO4), filtered and evaporated in vacuo. The residue obtained was purified by column chromatography (petroleum ether: EtOAc, 10:1 to 5:1, then DCM: MeOH, 20:1) to give the title compound as a yellow solid (436 mg 82%).

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. temperatureto warm to room temperature
  6. stirringwas stirred for 2 h
  7. extractionextracted with EtOAc
  8. washThe combined organic extracts were washed with water and brine
  9. dry with materialdried (Na2SO4)
  10. filtrationfiltered
  11. customevaporated in vacuo
  12. customThe residue obtained
  13. customwas purified by column chromatography (petroleum ether

出典と根拠

ORDレコード
ord-f060430cd1f54f93b973b7adb0f98274
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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