Disodium 2,3-dihydroxybutanedioate → Asenapine

HRID 253752

Reaktionsgleichung

Reaktionsgleichung von HRID 253752
[Cl-].[Al+3].[Cl-].[Cl-].[H-].[Al+3].[Li+].[H-].[H-].[H-].[Cl:11][C:12]1[CH:13]=[CH:14][C:15]2[O:26][C:25]3[CH:27]=[CH:28][CH:29]=[CH:30][C:24]=3[C@H:18]3[C:19](=O)[N:20]([CH3:22])[CH2:21][C@@H:17]3[C:16]=2[CH:31]=1.C(C(C(C([O-])=O)O)O)([O-])=O.[Na+].[Na+]>O1CCCC1>[Cl:11][C:12]1[CH:13]=[CH:14][C:15]2[O:26][C:25]3[CH:27]=[CH:28][CH:29]=[CH:30][C:24]=3[C@H:18]3[CH2:19][N:20]([CH3:22])[CH2:21][C@@H:17]3[C:16]=2[CH:31]=1

Komponenten

6

Edukt 4

HCID 13355Disodium 2,3-dihydroxybutanedioateHCID 6451240Aluminum(III) ChlorideHCID 21226445Aluminium lithium hydrideHCID 58729182(3aS,12bS)-5-chloro-2-methyl-2,3,3a,12b-tetrahydro-1H-dibenzo[2,3:6,7]oxepino[4,5-c]pyrrol-1-one

Produkt 1

HCID 163091AsenapineAusbeute 94,4 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel3×

Reaktionsbedingungen

Temperatur
0 °C

Versuchsvorschrift

Aluminum chloride (65.7 mg) was added in portions to tetrahydrofuran (5 mL) at 0° C. Under stirring a 10% solution of lithium aluminum hydride in tetrahydrofuran (1.35 mL) was slowly added while keeping the temperature below 10° C. The mixture was cooled to 0° C. and stirred for 15 minutes. A solution of trans-5-chloro-2,3,3a,12b-tetrahydro-2-methyl-1H-dibenz[2,3:6,7]oxepino[4,5-c]pyrrol-1-one (VII) (0.40 grams) in tetrahydrofuran (4 mL) was added to the mixture while keeping the temperature below 15° C. Stirring was continued for 2 hours at 10° C., whereupon 0.5 N sodium tartrate solution (15 mL) was added while keeping the temperature below 10° C. Stirring was continued for 15 minutes at 20° C. The salt layer was extracted twice with a toluene:ethyl acetate (8:2) mixture (25 mL).The combined organic layers were dried on magnesium sulphate, filtered and evaporated in vacuo to yield 0.36 grams (94%) of trans-5-chloro-2,3,3a,12b-tetrahydro-2-methyl-1H-dibenz[2,3:6,7]oxepino[4,5-c]pyrrole (A).

Aufarbeitung

  1. additionwas slowly added
  2. customthe temperature below 10° C
  3. customthe temperature below 15° C
  4. stirringStirring
  5. additionwas added
  6. customthe temperature below 10° C
  7. stirringStirring
  8. waitwas continued for 15 minutes at 20° C
  9. extractionThe salt layer was extracted twice with a toluene:ethyl acetate (8:2) mixture (25 mL).The combined organic layers
  10. customwere dried on magnesium sulphate
  11. filtrationfiltered
  12. customevaporated in vacuo

Quellen und Nachweise

ORD-Eintrag
ord-271921d71fbd4351b01e83f7027b0524
Quelldatensatz
uspto-grants-2011_01
Patentnummer
US07872147B2

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