Thionyl Chloride → 3-methoxycarbonyl-7-[3-(1-benzoylpiperidin-4-yl)-1-oxopropyl]-2,3,4,5-tetrahydro-1H-3-benzazepine

HRID 327400ノート

反応式

HRID 327400 の反応式
S(Cl)(Cl)=O.[C:5]([N:13]1[CH2:18][CH2:17][CH:16]([CH2:19][CH2:20][C:21]([OH:23])=O)[CH2:15][CH2:14]1)(=[O:12])[C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1.[CH3:24][O:25][C:26]([N:28]1[CH2:34][CH2:33][C:32]2[CH:35]=[CH:36][CH:37]=[CH:38][C:31]=2[CH2:30][CH2:29]1)=[O:27].[Cl-].[Al+3].[Cl-].[Cl-]>>[CH3:24][O:25][C:26]([N:28]1[CH2:34][CH2:33][C:32]2[CH:35]=[CH:36][C:37]([C:21](=[O:23])[CH2:20][CH2:19][CH:16]3[CH2:15][CH2:14][N:13]([C:5](=[O:12])[C:6]4[CH:7]=[CH:8][CH:9]=[CH:10][CH:11]=4)[CH2:18][CH2:17]3)=[CH:38][C:31]=2[CH2:30][CH2:29]1)=[O:27]

参加物

5

反応物 4

HCID 24386Thionyl ChlorideHCID 6451240Aluminum(III) ChlorideHCID 191084543-(1-Benzoylpiperidin-4-yl)propanoic acidHCID 22219599Methyl 1,2,4,5-tetrahydro-3h-3-benzazepine-3-carboxylate

生成物 1

HCID 191084353-methoxycarbonyl-7-[3-(1-benzoylpiperidin-4-yl)-1-oxopropyl]-2,3,4,5-tetrahydro-1H-3-benzazepine収率 83.5%

反応条件

温度
0 °C

実験手順

Under ice-cooling, 1.5 ml of thionyl chloride was added dropwise to 1.08 g (4.1 mmol.) of 3-(1-benzoylpiperidin-4-yl)propionic acid obtained in Reference Example 9. The mixture was stirred for 40 minutes at 0° C., then thionyl chloride was distilled off. The residue was dissolved in 20 ml of 1,2-dichloroethane, to which was added 0.81 g (3.9 mmol.) of 3- methoxycarbonyl-2,3,4,5-tetrahydro-1H-3-benzazepine obtained in Reference Example 10. To the mixture was added 1.75 g (13.1 mmol.) of aluminum chloride in small portions. The mixture was stirred for one hour at room temperature, then the reaction mixture was poured into ice-water and extracted with dichloromethane. The organic layers were combined and washed with water once, then dried over anhydrous sodium sulfate, followed by distilling off the solvent. Purification by means of a silica gel column chromatography gave 1.46 g (83%) of 3-methoxycarbonyl-7-[3-(1- benzoylpiperidin-4-yl)-1-oxopropyl]-2,3,4,5-tetrahydro-1H-3-benzazepine. Recrystallization from ethyl acetate --n-hexane gave colorless needles, m.p. 120°-123° C.

後処理

  1. temperatureUnder ice-cooling
  2. customobtained in Reference Example 9
  3. distillationthionyl chloride was distilled off
  4. dissolutionThe residue was dissolved in 20 ml of 1,2-dichloroethane, to which
  5. customobtained in Reference Example 10
  6. stirringThe mixture was stirred for one hour at room temperature
  7. extractionextracted with dichloromethane
  8. washwashed with water once
  9. dry with materialdried over anhydrous sodium sulfate
  10. distillationby distilling off the solvent
  11. customPurification by means of a silica gel column chromatography

出典と根拠

ORDレコード
ord-89673d05e9254e0a91ad50e4c63fab0f
出典データセット
uspto-grants-1993_12
特許番号
US05273974

反応ノート

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