Triethylamine → Sufentanil

HRID 2070052

Reaktionsgleichung

Reaktionsgleichung von HRID 2070052
[S:1]([C:5]1[CH:13]=[CH:12][C:8]([N+]([O-])=O)=[CH:7][CH:6]=1)(O)(=O)=O.[O:14]=[C:15]([N:18]([C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1)[C:19]1([CH2:25][O:26][CH3:27])[CH2:24][CH2:23][NH:22][CH2:21][CH2:20]1)[CH2:16][CH3:17].COC(C)(C)C.C(N(CC)CC)C>O>[CH3:17][CH2:16][C:15]([N:18]([C:19]1([CH2:25][O:26][CH3:27])[CH2:20][CH2:21][N:22]([CH2:7][CH2:6][C:5]2[S:1][CH:8]=[CH:12][CH:13]=2)[CH2:23][CH2:24]1)[C:28]1[CH:29]=[CH:30][CH:31]=[CH:32][CH:33]=1)=[O:14]

Komponenten

5

Edukt 3

HCID 8471TriethylamineHCID 15413tert-Butyl methyl ether2×HCID 131730047HCID 131730047, Verbindung

Produkt 1

HCID 41693SufentanilAusbeute 831,5 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 962WaterLösungsmittel

Reaktionsbedingungen

Temperatur
60 °C

Versuchsvorschrift

To a jacketed glass reactor with stirring, nitrogen blanket, internal temperature recorder, and reflux capabilities was charged 4-[(1-oxopropyl)phenylamino]-4-methoxymethyl piperidine nosylate (100.0 g, 21 mmol), 2-(2-thiophenylethyl) 4-nitro-benzene sulfonate (71.9 g, 23 mmol), tert-butyl methyl ether (MTBE, 222 g, 300 mL), and triethylamine (TEA, 436 g, 4.3 mol). The reaction mixture was warmed to 60±5° C. As the reaction progressed, a slurry was formed. After 5 hours, the system was cooled and charged with MTBE (296 g, 400 mL). This diluted system was washed sequentially with water (400 mL), 5% aqueous sodium bicarbonate (400 mL), water (400 mL), and water (400 mL). The solvent was removed by distillation and replaced with iso-propanol (394 g, 500 mL). The system was warmed to give a clear solution at 45° C. Water (800 g, 800 mL) was added to give a turbid system at 45° C. The hazy slurry was cooled slowly to ambient temperature, then further cooled to 5° C., and held at that temperature for approximately 15 hours. The resultant slurry was filtered and washed with 40% aqueous iso-propanol to provide white crystals. The solids were dried to constant weight under vacuum at 55° C. This process provided 67.5 g (84 mol %) of sufentanil as a white solid, purity over 99% by HPLC.

Aufarbeitung

  1. temperaturenitrogen blanket, internal temperature recorder, and reflux capabilities
  2. customa slurry was formed
  3. temperaturethe system was cooled
  4. washThis diluted system was washed sequentially with water (400 mL), 5% aqueous sodium bicarbonate (400 mL), water (400 mL), and water (400 mL)
  5. customThe solvent was removed by distillation
  6. temperatureThe system was warmed
  7. customto give a clear solution at 45° C
  8. customto give a turbid system at 45° C
  9. temperatureThe hazy slurry was cooled slowly to ambient temperature
  10. temperaturefurther cooled to 5° C.
  11. waitheld at that temperature for approximately 15 hours
  12. filtrationThe resultant slurry was filtered
  13. washwashed with 40% aqueous iso-propanol
  14. customto provide white crystals
  15. customThe solids were dried to constant weight under vacuum at 55° C

Quellen und Nachweise

ORD-Eintrag
ord-4fa02adafe204e56bdd0d769dcaa682a
Quelldatensatz
uspto-grants-2012_10
Patentnummer
US08299258B2

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