Phosphoric Acid → HCID 131737206, compound

HRID 63780Notes

Reaction equation

HRID 63780 reaction equation
[P:1](=[O:5])([OH:4])([OH:3])[OH:2].[CH3:6][N:7]1[CH2:24][CH:23]2[CH:9]([C:10]3[CH:11]=[CH:12][CH:13]=[CH:14][C:15]=3[O:16][C:17]3[CH:18]=[CH:19][C:20]([Cl:25])=[CH:21][C:22]=32)[CH2:8]1>C(O)C>[CH3:6][N:7]1[CH2:24][CH:23]2[CH:9]([C:10]3[CH:11]=[CH:12][CH:13]=[CH:14][C:15]=3[O:16][C:17]3[CH:18]=[CH:19][C:20]([Cl:25])=[CH:21][C:22]=32)[CH2:8]1.[P:1]([O-:5])([O-:4])([O-:3])=[O:2]

Participants

4

Reactant 2

HCID 1004Phosphoric AcidHCID 99039705-Chloro-2-methyl-2,3,3a,12b-tetrahydrodibenzo(2,3:6,7)oxepino(4,5-c)pyrrole

Product 1

HCID 131737206HCID 131737206, compoundYield 94%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent2×

Conditions

Temperature
50 °C

Procedure

0.69 Kg of asenapine maleate (1.69 moles) with a purity of 98% (HPLC) is loaded into a reactor. Toluene (7.2 L) is added, and the suspension is stirred at 25° C. A 9% solution of sodium bicarbonate (7.2 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 (2×3.6 L). The solvent is evaporated under vacuum, obtaining asenapine base (0.50 Kg) in the form of oil. 4.6 L of ethanol is added. The solution is stirred, heating to 50° C. An 85% solution of phosphoric acid (0.12 L, 1.69 moles) in ethanol (0.68 L) is dripped into the solution of asenapine base at 50° C. in 10 minutes. The solution is stirred for 30 minutes 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 ethanol (0.75 L). The product is dried under vacuum at 25° C. for 20 hours. 0.614 Kg of asenapine phosphate is obtained (yield=94.0%). Purity >99.5% (HPLC).

Workup

  1. stirringThe solution is stirred for 30 minutes at 50° C
  2. temperatureThe solution is cooled to 25° C. in approx. 2 hours
  3. waitThe solution is left
  4. stirringunder stirring at 25° C. for 2 hours
  5. customThe product is isolated by filtration
  6. washwashing with ethanol (0.75 L)
  7. customThe product is dried under vacuum at 25° C. for 20 hours

Sources & evidence

ORD record
ord-94dc0e7eb02743cba2e2891c32c5d908
Source dataset
uspto-grants-2016_09
Patent number
US09447109B2

Reaction notes

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