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 31520ノート

反応式

HRID 31520 の反応式
[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

参加物

7

反応物 5

HCID 6371PhosgeneHCID 8471Triethylamine2 回HCID 4207714-PiperidinemethanolHCID 516892Sodium BicarbonateHCID 101741684,5-bis-(4-chloro-phenyl)-2-(2-ethoxy-4-trifluoromethyl-phenyl)-4,5-dihydro-1H-imidazole

生成物 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]-methanone収率 79%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

反応条件

温度
0 °C

実験手順

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%).

後処理

  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

出典と根拠

ORDレコード
ord-f971cb0a9c4040a1a2b5d6be83785893
出典データセット
uspto-grants-2008_09
特許番号
US07425638B2

反応ノート

読み込み中…