Phosphoric Acid → HCID 131737206, compound

HRID 63778Notes

Reaction equation

HRID 63778 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:21](=[O:25])([OH:24])([OH:23])[OH:22]>C(O)C>[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:21]([O-:25])([O-:24])([O-:23])=[O:22]

Participants

4

Reactant 2

HCID 1004Phosphoric AcidHCID 99039705-Chloro-2-methyl-2,3,3a,12b-tetrahydrodibenzo(2,3:6,7)oxepino(4,5-c)pyrrole2×

Product 1

HCID 131737206HCID 131737206, compoundYield 105.9%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent2×

Conditions

Temperature
50 °C

Procedure

0.71 Kg of crude asenapine base (2.48 moles) and 6.7 L of ethanol are loaded into a reactor and dissolved by heating at 50° C. An 85% solution of phosphoric acid (0.17 L, 2.48 moles) in ethanol (1.0 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 (1.1 L). The product is dried under vacuum at 25° C. for 20 hours. 1 Kg of asenapine phosphate is obtained (yield=94.0%). Purity >99.5% (HPLC). The IR spectrum, the DSC thermogram and the XRPD spectrum of asenapine phosphate are shown in FIGS. 1, 2 and 3 respectively. Table 1 shows the Bragg 2-theta angles (2θ), interplanar distances d and the relative intensities expressed as a percentage of the most intense diffraction peak. Table 3 shows the improvement in the quality of the product, expressed as HPLC area %, obtained in the conversion from asenapine base to asenapine phosphate. In Table 3, RRT indicates the relative retention time of the impurities present in the product obtained, compared with the retention time of asenapine.

Workup

  1. dissolutiondissolved
  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 (1.1 L)
  7. customThe product is dried under vacuum at 25° C. for 20 hours

Sources & evidence

ORD record
ord-f4ad76cc9b4f4d50807b9df10fec7b62
Source dataset
uspto-grants-2016_09
Patent number
US09447109B2

Reaction notes

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