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

HRID 889536노트

반응식

HRID 889536 반응식
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]

참가 물질

6

반응물 4

HCID 8471TriethylamineHCID 14798Sodium HydroxideHCID 62325Isobutyryl chlorideHCID 67970562HCID 67970562, 화합물

생성물 1

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

시약·촉매·용매 1

HCID 6344Dichloromethane용매2회

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-0b6fa1aa20e54f0e82c9a1ba7ecd1f53
출처 데이터셋
uspto-grants-2012_08
특허 번호
US08252831B2

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