Potassium Iodide → tertbutyl 3(R)-[5-(1-benzyloxycarbonyl-4-piperidyl)-1(S)-ethoxycarbonylpentyl]amino-4-oxo-2,3,4,5-tetrahydro-1,5-benzothiazepine-5-acetate

HRID 649408Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 649408
[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(#N)C.[CH2:25]([O:32][C:33]([N:35]1[CH2:40][CH2:39][CH:38]([CH2:41][CH2:42][CH2:43][CH2:44][CH:45](Cl)[C:46]([O:48][CH2:49][CH3:50])=[O:47])[CH2:37][CH2:36]1)=[O:34])[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1.[I-].[K+]>C(N(CC)CC)C>[CH2:25]([O:32][C:33]([N:35]1[CH2:36][CH2:37][CH:38]([CH2:41][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])[CH2:39][CH2:40]1)=[O:34])[C:26]1[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=1.[CH2:25]([O:32][C:33]([N:35]1[CH2:36][CH2:37][CH:38]([CH2:41][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])[CH2:39][CH2:40]1)=[O:34])[C:26]1[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=1

Komponenten

7

Edukt 4

HCID 4875Potassium Iodide2×HCID 6342AcetonitrileHCID 13454543tert-butyl 3(R)-amino-4-oxo-2,3,4,5-tetrahydro-1,5-benzothiazepine-5-acetateHCID 19868892Ethyl 6-(1-benzyloxycarbonyl-4-piperidyl)-2-chlorohexanoate2×

Produkt 2

HCID 54276749tertbutyl 3(R)-[5-(1-benzyloxycarbonyl-4-piperidyl)-1(S)-ethoxycarbonylpentyl]amino-4-oxo-2,3,4,5-tetrahydro-1,5-benzothiazepine-5-acetateHCID 54276750tert-butyl 3(R)-[5-(1-benzyloxycarbonyl-4-piperidyl)-1(R)-ethoxycarbonylpentyl]amino-4-oxo-2,3,4,5-tetrahydro-1,5-benzothiazepine-5-acetate

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8471TriethylamineLösungsmittel

Reaktionsbedingungen

Temperatur
80 °C

Versuchsvorschrift

A mixture of tert-butyl 3(R)-amino-4-oxo-2,3,4,5-tetrahydro-1,5-benzothiazepine-5-acetate (3.0 g), acetonitrile (100 ml), ethyl 6-(1-benzyloxycarbonyl-4-piperidyl)-2-chlorohexanoate (4.0 g), triethylamine (1.0 g) and potassium iodide (1.6 g) is stirred for 3 days at 80° C. Ethyl 6-(1-benzyloxycarbonyl-4-piperidyl)-2-chlorohexanoate (2.0 g) and potassium iodide (0.8 g) are added, and the stirring is continued for further 1 day at 80° C. The mixture is concentrated in vacuo, diluted with water (100 ml) and extracted with ethyl acetate (300 ml). The extract is washed with water, dried over anhydrous magnesium sulfate and evaporated in vacuo. Purification of the residual oil by silicagel column chromatography (hexane:ethyl acetate=2:1) gives tert-butyl 3(R)-[5-(1-benzyloxycarbonyl-4-piperidyl)-1(R)-ethoxycarbonylpentyl]amino-4-oxo-2,3,4,5-tetrahydro-1,5-benzothiazepine-5-acetate (3.1 g) as a colorless oil and tert-butyl 3(R)-[5-(1-benzyloxycarbonyl-4-piperidyl)-1 (S)-ethoxycarbonylpentyl]amino-4-oxo-2,3,4,5-tetrahydro-1,5-benzothiazepine-5-acetate (2.1 g) as a colorless oil.

Aufarbeitung

  1. waitthe stirring is continued for further 1 day at 80° C
  2. concentrationThe mixture is concentrated in vacuo
  3. additiondiluted with water (100 ml)
  4. extractionextracted with ethyl acetate (300 ml)
  5. washThe extract is washed with water
  6. dry with materialdried over anhydrous magnesium sulfate
  7. customevaporated in vacuo
  8. customPurification of the residual oil by silicagel column chromatography (hexane:ethyl acetate=2:1)

Quellen und Nachweise

ORD-Eintrag
ord-abfa6d969662415fa9094940353603d2
Quelldatensatz
uspto-grants-1988_04
Patentnummer
US04739066

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