Desipramine → 3-{[3-(10,11-dihydro-dibenzo[b,f]azepine-5-yl)-propyl]-methyl-amino}-propionic Acid Ethyl Ester

HRID 840509

反応式

HRID 840509 の反応式
[CH3:1][NH:2][CH2:3][CH2:4][CH2:5][N:6]1[C:16]2[CH:17]=[CH:18][CH:19]=[CH:20][C:15]=2[CH2:14][CH2:13][C:12]2[CH:11]=[CH:10][CH:9]=[CH:8][C:7]1=2.[CH2:21]([O:23][C:24](=[O:28])[CH2:25][CH2:26]Br)[CH3:22].C(=O)([O-])[O-].[K+].[K+].[I-].[Na+]>CC(C)=O.C1OCCOCCOCCOCCOCCOC1.CN(C=O)C>[CH2:21]([O:23][C:24](=[O:28])[CH2:25][CH2:26][N:2]([CH2:3][CH2:4][CH2:5][N:6]1[C:7]2[CH:8]=[CH:9][CH:10]=[CH:11][C:12]=2[CH2:13][CH2:14][C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][C:16]1=2)[CH3:1])[CH3:22]

参加物

8

反応物 4

HCID 2995DesipramineHCID 5238Sodium IodideHCID 11430Potassium CarbonateHCID 68320Ethyl 3-bromopropionate

生成物 1

HCID 691417273-{[3-(10,11-dihydro-dibenzo[b,f]azepine-5-yl)-propyl]-methyl-amino}-propionic Acid Ethyl Ester収率 89%

試薬・触媒・溶媒 3

HCID 2855718-Crown-6触媒HCID 180Acetone溶媒HCID 6228Dimethylformamide溶媒

実験手順

A solution of 6.02 g (19.8 mmol) of desipramine hydrochloride was allowed to stir at room temperature for 5 minutes. This was extracted with 6×100 ml of chloroform. The combined organic part was washed with 100 ml of water, dried with anhydrous Na2SO4 and concentrated to give 5.25 g of desipramine free base. A solution of 2.82 g (10.6 mmol) of desipramine free base in 100 ml of anhydrous acetone was added. To this reaction mixture 2.03 ml (15.8 mmol) of ethyl-3-bromopropionate, 3.65 g (26.4 mmol) of anhydrous potassium carbonate, 264 mg (1.76 mmol) of sodium iodide, 5 mg of 18-crown-6 and 0.7 ml of anhydrous DMF were added. The reaction mixture was allowed to reflux under argon overnight. The mixture was filtered and the residue was washed with 20 ml of acetone. The combined filtrate was concentrated and purified by silica gel column chromatography using 4% methanol in ethyl acetate to give 3.45 g (9.41 mmol, 89%) of the ethyl ester (17) as a thick oil.

後処理

  1. temperatureto reflux under argon overnight
  2. filtrationThe mixture was filtered
  3. washthe residue was washed with 20 ml of acetone
  4. concentrationThe combined filtrate was concentrated
  5. custompurified by silica gel column chromatography

出典と根拠

ORDレコード
ord-4a2d670f8ff74230a476fa42fde86bb6
出典データセット
uspto-grants-2002_04
特許番号
US06368814B1

関連ノート

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