Methanesulfonyl chloride → Naltrexone Base

HRID 1037634

Reaktionsgleichung

Reaktionsgleichung von HRID 1037634
CS(Cl)(=O)=O.[CH:6]1([CH2:9]O)[CH2:8][CH2:7]1.[Br-].[Li+].[O:13]1[C@@H:25]2[C@@:26]34[CH2:28][CH2:29][NH:30][C@@H:20]([C@:21]3([OH:32])[CH2:22][CH2:23][C:24]2=[O:31])[CH2:19][C:18]2=[C:27]4[C:14]1=[C:15]([OH:33])[CH:16]=[CH:17]2>CN(C=O)C.C(N(CC)CC)C>[CH2:7]1[CH:6]([CH2:9][N:30]2[C@@H:20]3[CH2:19][C:18]4[CH:17]=[CH:16][C:15]([OH:33])=[C:14]5[O:13][CH:25]6[C:24]([CH2:23][CH2:22][C@:21]3([OH:32])[C@:26]6([C:27]=45)[CH2:28][CH2:29]2)=[O:31])[CH2:8]1

Komponenten

7

Edukt 4

HCID 31297Methanesulfonyl chlorideHCID 75644CyclopropanemethanolHCID 82050Lithium BromideHCID 5497189(-)-Noroxymorphone

Produkt 1

HCID 21159611Naltrexone Base

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6228DimethylformamideLösungsmittelHCID 8471TriethylamineLösungsmittel

Reaktionsbedingungen

Temperatur
2.5 °C

Versuchsvorschrift

Methanesulphonyl chloride (76 kg) was added to the mixture of cyclopropyl methanol (50 kg) and triethylamine (192 L) in DMF (400 L) maintained at 0-5° C., the reaction mixture was maintained at 0-5° C. for 3.0 hrs. Lithium bromide (60 Kg) was added to reaction mixture at 0-15° C. and maintained for 10-15 minutes. Noroxymorphone (40 Kg) was added to above reaction mixture at 0-5° C. and temperature raised to 65-70° C. over 1.0 hr period and maintained for 14-15 hrs. After completion of reaction it was quenched in ice-water below 20° C. and the product was extracted with ethylacetate. The ethylacetate layer was concentrated and the product was isolated with MDC and cyclohexane mixture at 10-15° C. Yield=35.3 Kg.

Aufarbeitung

  1. temperaturethe reaction mixture was maintained at 0-5° C. for 3.0 hrs
  2. temperaturemaintained for 10-15 minutes
  3. temperaturetemperature raised to 65-70° C. over 1.0 hr period
  4. temperaturemaintained for 14-15 hrs
  5. customAfter completion of reaction it
  6. customwas quenched in ice-water below 20° C.
  7. extractionthe product was extracted with ethylacetate
  8. concentrationThe ethylacetate layer was concentrated
  9. customthe product was isolated with MDC and cyclohexane mixture at 10-15° C

Quellen und Nachweise

ORD-Eintrag
ord-748ef38b5eb940419edd21c83897d8c9
Quelldatensatz
uspto-grants-2013_10
Patentnummer
US08546572B2

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