Sodium Iodide → Tert-butyl 4-[1-(2-pyrrolidin-1-ylethyl)-4-tetrahydropyran-4-yl-imidazol-2-yl]piperidine-1-carboxylate

HRID 2088913ノート

反応式

HRID 2088913 の反応式
[O:1]1[CH2:6][CH2:5][CH:4]([C:7]2[N:8]=[C:9]([CH:12]3[CH2:17][CH2:16][N:15]([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH2:14][CH2:13]3)[NH:10][CH:11]=2)[CH2:3][CH2:2]1.[OH-].[K+].[I-].[Na+].[Cl-].Cl[CH2:31][CH2:32][NH+:33]1[CH2:37][CH2:36][CH2:35][CH2:34]1>CS(C)=O>[O:1]1[CH2:6][CH2:5][CH:4]([C:7]2[N:8]=[C:9]([CH:12]3[CH2:13][CH2:14][N:15]([C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH2:16][CH2:17]3)[N:10]([CH2:31][CH2:32][N:33]3[CH2:37][CH2:36][CH2:35][CH2:34]3)[CH:11]=2)[CH2:3][CH2:2]1

参加物

6

反応物 4

HCID 5238Sodium IodideHCID 14797Potassium HydroxideHCID 110083391-(2-Chloroethyl)pyrrolidine HydrochlorideHCID 178451797HCID 178451797、化合物

生成物 1

HCID 67112170Tert-butyl 4-[1-(2-pyrrolidin-1-ylethyl)-4-tetrahydropyran-4-yl-imidazol-2-yl]piperidine-1-carboxylate収率 63%

試薬・触媒・溶媒 1

HCID 679Dimethyl Sulfoxide溶媒2 回

実験手順

Combine tert-butyl 4-(4-(tetrahydro-2H-pyran-4-yl)-1H-imidazol-2-yl)piperidine-1-carboxylate (101.10 g, 301.39 mmol) and freshly ground potassium hydroxide (50.73 g, 3.0 eq) in dimethyl sulfoxide (500 mL). Stir for 15 minutes, then add sodium iodide (49.69 g, 1.1 eq). Add a solution of 1-(2-chloro-ethyl)-pyrrolidinium chloride (66.64 g, 1.3 eq) in dimethyl sulfoxide (1.01 L) and stir for four hours at room temperature. Pour the contents of the reaction into an ice/water mixture (˜1 L) and extract with methyl tert-butyl ether. Dry the organics over anhydrous magnesium sulfate, filter, and concentrate in vacuo. Purify by HPLC (Chiralpak AD basic, hexane/ethanol 9:1) to give tert-butyl 4-(4-(tetrahydro-2H-pyran-4-yl)-1-(2-(pyrrolidin-1-yl)ethyl)-1H-imidazol-2-yl)piperidine-1-carboxylate (82.0 g, 63%). MS (ES) m/z=433 [M]+.

後処理

  1. stirringstir for four hours at room temperature
  2. additionPour
  3. extractionextract with methyl tert-butyl ether
  4. dry with materialDry the organics over anhydrous magnesium sulfate
  5. filtrationfilter
  6. concentrationconcentrate in vacuo
  7. customPurify by HPLC (Chiralpak AD basic, hexane/ethanol 9:1)

出典と根拠

ORDレコード
ord-fa8e2333117142fab376dc33c29fcd72
出典データセット
uspto-grants-2013_05
特許番号
US08436002B2

反応ノート

読み込み中…