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Acetic Acid → tert-butyl 3(R)-[4-(1-benzyloxycarbonyl-4-piperidyl)-1(R)-ethoxycarbonylbutyl]amino-4-oxo-2,3,4,5-tetrahydro-1,5-benzothiazepine-5-acetate

HRID 980596
ノート
印刷プレビュー

反応式

HRID 980596 の反応式
[NH2:1][C@@H:2]1[C:8](=[O:9])[N:7]([CH2:10][C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])[C:6]2[CH:18]=[CH:19][CH:20]=[CH:21][C:5]=2[S:4][CH2:3]1.C(O)(=O)C.[CH2:26]([O:33][C:34]([N:36]1[CH2:41][CH2:40][CH:39]([CH2:42][CH2:43][CH2:44][C:45](=O)[C:46]([O:48][CH2:49][CH3:50])=[O:47])[CH2:38][CH2:37]1)=[O:35])[C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1.C([BH3-])#N.[Na+]>C(O)C>[CH2:26]([O:33][C:34]([N:36]1[CH2:37][CH2:38][CH:39]([CH2:42][CH2:43][CH2:44][C@@H:45]([NH:1][C@@H:2]2[C:8](=[O:9])[N:7]([CH2:10][C:11]([O:13][C:14]([CH3:16])([CH3:17])[CH3:15])=[O:12])[C:6]3[CH:18]=[CH:19][CH:20]=[CH:21][C:5]=3[S:4][CH2:3]2)[C:46]([O:48][CH2:49][CH3:50])=[O:47])[CH2:40][CH2:41]1)=[O:35])[C:27]1[CH:28]=[CH:29][CH:30]=[CH:31][CH:32]=1
参加物実験手順後処理出典と根拠反応ノート

参加物

6

反応物 4

HCID 176Acetic AcidHCID 5003444Sodium cyanoborohydrideHCID 13454543tert-butyl 3(R)-amino-4-oxo-2,3,4,5-tetrahydro-1,5-benzothiazepine-5-acetateHCID 14855086Ethyl 5-(1-benzyloxycarbonyl-4-piperidyl)-2-oxovalerate

生成物 1

HCID 54047948tert-butyl 3(R)-[4-(1-benzyloxycarbonyl-4-piperidyl)-1(R)-ethoxycarbonylbutyl]amino-4-oxo-2,3,4,5-tetrahydro-1,5-benzothiazepine-5-acetate
収率 9%

試薬・触媒・溶媒 1

HCID 702Ethanol溶媒2 回

実験手順

In 30 ml of ethanol is dissolved 2.1 g of tert-butyl 3(R)-amino-4-oxo-2,3,4,5-tetrahydro-1,5-benzothiazepine-5acetate, and 0.4 g of acetic acid, 2.5 g of ethyl 5-(1-benzyloxycarbonyl-4-piperidyl)-2-oxovalerate and 10 g of Molecular sieve 3A are added to the solution. The mixture is stirred at room temperature for 20 minutes, and a solution of 0.4 g of sodium cyanoborohydride in 50 ml of ethanol is added dropwise to the mixture at room temperature with stirring over the period of 3 hours. The reaction solution is allowed to stand at room temperature overnight, and concentrated under reduced pressure, and 300 ml of water and 300 ml of ethyl acetate are added to the residue, followed by shaking. The insoluble matter is removed by filtration, and the ethyl acetate layer is dried over anhydrous magnesium sulfate and ccncentrated under reduced pressure. Ethyl acetate (20 ml) and 2 g of oxalic acid are added to the residue, and the mixture is shaken thoroughly and admixed with 300 ml of petroleum ether, followed by allowing the mixture to stand. The solution portion is removed by decantation, and 100 ml of water and 200 ml of ethyl acetate are added to the precipitate portion, followed by adding excess sodium hydrogencarbonate to conduct neutralization. The ethyl acetate layer is dried over anhydrous magnesium sulfate and concentrated under reduced pressure to give an oily material. This product is separated and purified by silica-gel column chromatography (hexane:ethyl acetate=2:1) to give from the first fraction 0.4 g of tert-butyl 3(R)-[4-(1-benzyloxycarbonyl-4-piperidyl)-1(R)-ethoxycarbonylbutyl]amino-4-oxo-2,3,4,5-tetrahydro-1,5-benzothiazepine-5-acetate as a colorless oily material.

後処理

  1. additionare added to the solution
  2. stirringwith stirring over the period of 3 hours
  3. waitto stand at room temperature overnight
  4. concentrationconcentrated under reduced pressure, and 300 ml of water and 300 ml of ethyl acetate
  5. additionare added to the residue
  6. stirringby shaking
  7. customThe insoluble matter is removed by filtration
  8. dry with materialthe ethyl acetate layer is dried over anhydrous magnesium sulfate
  9. additionEthyl acetate (20 ml) and 2 g of oxalic acid are added to the residue
  10. stirringthe mixture is shaken thoroughly
  11. customThe solution portion is removed by decantation, and 100 ml of water and 200 ml of ethyl acetate
  12. additionare added to the precipitate portion
  13. additionby adding excess sodium hydrogencarbonate
  14. dry with materialThe ethyl acetate layer is dried over anhydrous magnesium sulfate
  15. concentrationconcentrated under reduced pressure
  16. customto give an oily material
  17. customThis product is separated
  18. custompurified by silica-gel column chromatography (hexane:ethyl acetate=2:1)

出典と根拠

ORDレコード
ord-3371dfa3ddf14147a0e0cccb7745e82f
出典データセット
uspto-grants-1987_01
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US04638000

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