Phosgene → [4,5-Bis-(4-chloro-phenyl)-2-(2-ethoxy-4-trifluoromethyl-phenyl)-4,5-dihydro-imidazol-1-yl]-[4-hydroxymethyl-piperidin-1-yl]-methanone

HRID 31520노트

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HRID 31520 반응식
[C:1](Cl)(Cl)=[O:2].C(N(CC)CC)C.[Cl:12][C:13]1[CH:18]=[CH:17][C:16]([CH:19]2[CH:23]([C:24]3[CH:29]=[CH:28][C:27]([Cl:30])=[CH:26][CH:25]=3)[NH:22][C:21]([C:31]3[CH:36]=[CH:35][C:34]([C:37]([F:40])([F:39])[F:38])=[CH:33][C:32]=3[O:41][CH2:42][CH3:43])=[N:20]2)=[CH:15][CH:14]=1.[OH:44][CH2:45][CH:46]1[CH2:51][CH2:50][NH:49][CH2:48][CH2:47]1.C(=O)(O)[O-].[Na+]>C(Cl)Cl>[Cl:12][C:13]1[CH:14]=[CH:15][C:16]([CH:19]2[CH:23]([C:24]3[CH:25]=[CH:26][C:27]([Cl:30])=[CH:28][CH:29]=3)[N:22]([C:1]([N:49]3[CH2:50][CH2:51][CH:46]([CH2:45][OH:44])[CH2:47][CH2:48]3)=[O:2])[C:21]([C:31]3[CH:36]=[CH:35][C:34]([C:37]([F:38])([F:39])[F:40])=[CH:33][C:32]=3[O:41][CH2:42][CH3:43])=[N:20]2)=[CH:17][CH:18]=1

참가 물질

7

반응물 5

HCID 6371PhosgeneHCID 8471Triethylamine2회HCID 4207714-PiperidinemethanolHCID 516892Sodium BicarbonateHCID 101741684,5-bis-(4-chloro-phenyl)-2-(2-ethoxy-4-trifluoromethyl-phenyl)-4,5-dihydro-1H-imidazole

생성물 1

HCID 69273741[4,5-Bis-(4-chloro-phenyl)-2-(2-ethoxy-4-trifluoromethyl-phenyl)-4,5-dihydro-imidazol-1-yl]-[4-hydroxymethyl-piperidin-1-yl]-methanone수율 79%

시약·촉매·용매 1

HCID 6344Dichloromethane용매

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온도
0 °C

실험 절차

Phosgene (1.8 mL, 3.6 mmol, 1.9 M in toluene) was added dropwise to a cooled (0° C.) solution of triethylamine (0.57 mL, 4.0 mmol) and 4,5-bis-(4-chloro-phenyl)-2-(2-ethoxy-4-trifluro-phenyl)-4,5-dihydro-1H-imidazole (550 mg, 1.2 mmol, example 1) in methylene chloride (5.0 mL). The reaction mixture was stirred for 0.5 h at 0° C. The solvent was removed under reduced pressure. The residue was kept under high vacuum for 30 min and dissolved in methylene chloride (5.0 mL). Triethylamine (0.170, 1.2 mmol) and 4-(hydroxymethyl)piperidine (0.50 g, 4.4 mmol) were added. After 1 h, the reaction was worked up with aqueous sodium bicarbonate and extracted with methylene chloride. The organic extracts were washed with brine and dried over anhydrous sodium sulfate. Evaporation of the solvents and flash chromatography of the residue over silica gel using 1-4% methanol in methylene chloride gave [4,5-bis-(4-chloro-phenyl)-2-(2-ethoxy-4-trifluoromethyl-phenyl)-4,5-dihydro-imidazol-1-yl]-[4-hydroxymethyl-piperidin-1-yl]-methanone (560 mg, 79%).

후처리

  1. customThe solvent was removed under reduced pressure
  2. waitThe residue was kept under high vacuum for 30 min
  3. dissolutiondissolved in methylene chloride (5.0 mL)
  4. waitAfter 1 h
  5. extractionextracted with methylene chloride
  6. washThe organic extracts were washed with brine
  7. dry with materialdried over anhydrous sodium sulfate
  8. customEvaporation of the solvents and flash chromatography of the residue over silica gel using 1-4% methanol in methylene chloride

출처 및 근거

ORD 기록
ord-f971cb0a9c4040a1a2b5d6be83785893
출처 데이터셋
uspto-grants-2008_09
특허 번호
US07425638B2

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