Sodium → 1,1-Dioxo-3-butyl-3-ethyl-5-phenyl-7-isopropoxy-8-carboxymethoxy-2,3,4,5-tetrahydro-1,5-benzothiazepine

HRID 458918Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 458918
[Na].[O:2]=[S:3]1(=[O:32])[C:9]2[CH:10]=[C:11]([O:15][CH2:16][C:17]([OH:19])=[O:18])[C:12](Br)=[CH:13][C:8]=2[N:7]([C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[CH2:6][C:5]([CH2:28][CH2:29][CH2:30][CH3:31])([CH2:26][CH3:27])[CH2:4]1>C(O)(C)C>[O:2]=[S:3]1(=[O:32])[C:9]2[CH:10]=[C:11]([O:15][CH2:16][C:17]([OH:19])=[O:18])[C:12]([O:15][CH:11]([CH3:12])[CH3:10])=[CH:13][C:8]=2[N:7]([C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[CH2:6][C:5]([CH2:28][CH2:29][CH2:30][CH3:31])([CH2:26][CH3:27])[CH2:4]1

Komponenten

4

Edukt 2

HCID 5360545Sodium2×HCID 223931311,1-Dioxo-3-butyl-3-ethyl-5-phenyl-7-bromo-8-carboxymethoxy-2,3,4,5-tetrahydro-1,5-benzothiazepine

Produkt 1

HCID 184424731,1-Dioxo-3-butyl-3-ethyl-5-phenyl-7-isopropoxy-8-carboxymethoxy-2,3,4,5-tetrahydro-1,5-benzothiazepineAusbeute 81,7 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 3776IsopropanolLösungsmittel

Reaktionsbedingungen

Temperatur
80 °C

Versuchsvorschrift

To isopropyl alcohol (12 ml) was added sodium (115 mg, 5 mmol) and the temperature was then raised to 80° C. to let the alcohol salt form. After all the sodium was dissolved 1,1-dioxo-3-butyl-3-ethyl-5-phenyl-7-bromo-8-carboxymethoxy-2,3,4,5-tetrahydro-1,5-benzothiazepine (Method 9; 100 mg, 0.2 mmol) was added in one portion. The reaction was then refluxed overnight, and then cooled to room temperature and quenched with acetic acid. The solvent was then removed under reduced pressure and the residue was dissolved in water and MeCN (70/30) and partially purified by HPLC. The residue was dissolved in ethylene glycol and NaOH (500 mg) was added. This reaction mixture was heated to 125° C. overnight and then cooled to room temperature and quenched with acetic acid, and EtOAc (100 ml) was added. The ethylene glycol was removed by washing the organic layer with acidic water three times. The organic layer was then concentrated and the residue was purified again as above to give the title compound 40 mg (41%). NMR (300 MHz) 0.7–1.0 (m, 6H), 1.0–1.8 (m, 15H), 3.2 (q, 2H), 3.75 (m, 2H), 4.3 (m, 1H), 4.6 (s, 2H), 6.35 (s, 1H), 6.95–7.2 (m, 3H), 7.2–7.4 (m, 2H), 7.55 (s, 1H).

Aufarbeitung

  1. additionwas added in one portion
  2. temperatureThe reaction was then refluxed overnight
  3. temperaturecooled to room temperature
  4. customquenched with acetic acid
  5. customThe solvent was then removed under reduced pressure
  6. dissolutionthe residue was dissolved in water
  7. customMeCN (70/30) and partially purified by HPLC
  8. dissolutionThe residue was dissolved in ethylene glycol
  9. additionNaOH (500 mg) was added
  10. temperatureThis reaction mixture was heated to 125° C. overnight
  11. temperaturecooled to room temperature
  12. customquenched with acetic acid, and EtOAc (100 ml)
  13. additionwas added
  14. customThe ethylene glycol was removed
  15. washby washing the organic layer with acidic water three times
  16. concentrationThe organic layer was then concentrated
  17. customthe residue was purified again as above

Quellen und Nachweise

ORD-Eintrag
ord-0a4016f7e3f540a3abba967f27b967fc
Quelldatensatz
uspto-grants-2007_03
Patentnummer
US07192945B2

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