Sodium Bicarbonate → 5-Chloro-2-methyl-2,3,3a,12b-tetrahydrodibenzo(2,3:6,7)oxepino(4,5-c)pyrrole

HRID 63781Notes

Reaction equation

HRID 63781 reaction equation
[CH3:1][N:2]1[CH2:19][CH:18]2[CH:4]([C:5]3[CH:6]=[CH:7][CH:8]=[CH:9][C:10]=3[O:11][C:12]3[CH:13]=[CH:14][C:15]([Cl:20])=[CH:16][C:17]=32)[CH2:3]1.P([O-])([O-])([O-])=O.C(=O)(O)[O-].[Na+]>C1(C)C=CC=CC=1>[CH3:1][N:2]1[CH2:19][CH:18]2[CH:4]([C:5]3[CH:6]=[CH:7][CH:8]=[CH:9][C:10]=3[O:11][C:12]3[CH:13]=[CH:14][C:15]([Cl:20])=[CH:16][C:17]=32)[CH2:3]1

Participants

4

Reactant 2

HCID 516892Sodium BicarbonateHCID 131737206HCID 131737206, compound

Product 1

HCID 99039705-Chloro-2-methyl-2,3,3a,12b-tetrahydrodibenzo(2,3:6,7)oxepino(4,5-c)pyrroleYield 86.9%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

1.38 Kg of asenapine phosphate is loaded into a reactor. Toluene (15 L) is added, and the suspension is placed under stirring. A 9% solution of sodium bicarbonate (15 L) is added by dripping. The solution is left under stirring at 25° C. for 30 minutes. The lower aqueous phase is eliminated. The organic phase is washed with water (2×7 L). The solvent is evaporated under vacuum, obtaining asenapine base (0.90 Kg) in the form of oil. Isopropanol (12 L) is loaded into the reactor and dissolved by heating at 50° C. Maleic acid (0.4 Kg) is added to the asenapine base solution at 50° C. The solution is cooled to 25° C. in approx. 2 hours. The solution is left under stirring at 25° C. for 2 hours. The product is isolated by filtration, washing with isopropanol (3 L). The product is dried under vacuum at 50° C. for 20 hours. 1 Kg of asenapine maleate is obtained.

Workup

  1. waitThe solution is left
  2. stirringunder stirring at 25° C. for 30 minutes
  3. washThe organic phase is washed with water (2×7 L)
  4. customThe solvent is evaporated under vacuum

Sources & evidence

ORD record
ord-ad2b736c6da045dd9bb988a063e0c2f6
Source dataset
uspto-grants-2016_09
Patent number
US09447109B2

Reaction notes

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