Triethylamine → 2-(Difluoromethyl)-5-[[(2-methyl-1-oxopropyl)amino]methyl]benzoic acid

HRID 889536ノート

反応式

HRID 889536 の反応式
Cl.[NH2:2][CH2:3][C:4]1[CH:5]=[CH:6][C:7]([CH:14]([F:16])[F:15])=[C:8]([CH:13]=1)[C:9]([O:11]C)=[O:10].C(N(CC)CC)C.[C:24](Cl)(=[O:28])[CH:25]([CH3:27])[CH3:26].[OH-].[Na+]>ClCCl>[F:15][CH:14]([F:16])[C:7]1[CH:6]=[CH:5][C:4]([CH2:3][NH:2][C:24](=[O:28])[CH:25]([CH3:27])[CH3:26])=[CH:13][C:8]=1[C:9]([OH:11])=[O:10]

参加物

6

反応物 4

HCID 8471TriethylamineHCID 14798Sodium HydroxideHCID 62325Isobutyryl chlorideHCID 67970562HCID 67970562、化合物

生成物 1

HCID 679705062-(Difluoromethyl)-5-[[(2-methyl-1-oxopropyl)amino]methyl]benzoic acid収率 94.1%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒2 回

実験手順

To a mixture of methyl 5-(aminomethyl)-2-(difluoromethyl)benzoate hydrochloride (1.30 g, 5.17 mmol, 1.0 equiv) and triethylamine (1.51 mL, 10.85 mmol, 2.1 equiv) in dichloromethane (50 mL) at room temperature, add isobutyryl chloride (0.571 mL, 5.42 mmol, 1.05 equiv) and stir for one hour. Dilute the mixture with dichloromethane and wash with water then saturated aqueous NaCl. Separate the organic layer and dry over sodium sulfate, filter, and concentrate under reduced pressure. Dissolve the resulting crude material in 1,4-dioxane (10 mL), and add sodium hydroxide (5 N aqueous, 2 mL, 10 mmol, 1.93 equiv). Stir the resulting suspension at 40° C. overnight. Concentrate the mixture under reduced pressure, and treat the resulting residue with 1 N aqueous hydrochloric acid until the pH reaches 3. Extract the resulting suspension with EtOAc (2×30 mL). Wash the combined organic layers with saturated aqueous NaCl (50 mL), dry over sodium sulfate, filter, and concentrate under reduced pressure to give the title compound as a white solid (1.32 g, 94%). MS (m/z) 272 (M+1).

後処理

  1. washwash with water
  2. customSeparate the organic layer
  3. dry with materialdry over sodium sulfate
  4. filtrationfilter
  5. concentrationconcentrate under reduced pressure
  6. dissolutionDissolve the resulting crude material in 1,4-dioxane (10 mL)
  7. stirringStir the resulting suspension at 40° C. overnight
  8. concentrationConcentrate the mixture under reduced pressure
  9. additiontreat the resulting residue with 1 N aqueous hydrochloric acid until the pH
  10. extractionExtract the resulting suspension with EtOAc (2×30 mL)
  11. washWash the combined organic layers with saturated aqueous NaCl (50 mL)
  12. dry with materialdry over sodium sulfate
  13. filtrationfilter
  14. concentrationconcentrate under reduced pressure

出典と根拠

ORDレコード
ord-0b6fa1aa20e54f0e82c9a1ba7ecd1f53
出典データセット
uspto-grants-2012_08
特許番号
US08252831B2

反応ノート

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