Phosphoric Acid → (3-cyano-1H-indol-7-yl)-[4-(4-fluorophenethyl)piperazin-1-yl]-methanone phosphate hydrate

HRID 1929412

Reaction equation

HRID 1929412 reaction equation
[C:1]([C:3]1[C:11]2[C:6](=[C:7]([C:12]([N:14]3[CH2:19][CH2:18][N:17]([CH2:20][CH2:21][C:22]4[CH:27]=[CH:26][C:25]([F:28])=[CH:24][CH:23]=4)[CH2:16][CH2:15]3)=[O:13])[CH:8]=[CH:9][CH:10]=2)[NH:5][CH:4]=1)#[N:2].[P:29](=[O:33])([OH:32])([OH:31])[OH:30]>C(O)C>[OH2:13].[P:29]([OH:33])([OH:32])([OH:31])=[O:30].[C:1]([C:3]1[C:11]2[C:6](=[C:7]([C:12]([N:14]3[CH2:15][CH2:16][N:17]([CH2:20][CH2:21][C:22]4[CH:23]=[CH:24][C:25]([F:28])=[CH:26][CH:27]=4)[CH2:18][CH2:19]3)=[O:13])[CH:8]=[CH:9][CH:10]=2)[NH:5][CH:4]=1)#[N:2]

Participants

4

Reactant 2

HCID 1004Phosphoric AcidHCID 6433122Pruvanserin

Product 1

HCID 68837267(3-cyano-1H-indol-7-yl)-[4-(4-fluorophenethyl)piperazin-1-yl]-methanone phosphate hydrateYield 188.5%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
75 °C

Procedure

Add (3-cyano-1H-indol-7-yl)-[4-(4-fluorophenethyl)piperazin-1-yl]methanone (300.0 g, 797 mmol.) and anhydrous ethanol (15 L, denatured with toluene) to a 22 L flask equipped with overhead agitation, heating mantle, and condenser. Heat the slurry to about 75° C. to provide a homogeneous solution. Add a solution of 1 M aqueous phosphoric acid (877 mL, 877 mmol, 1.1 equiv) over 10 minutes while maintaining the temperature above 72° C. The salt may begin precipitating after approximately 380 mL of phosphoric acid solution is added. Remove the heating mantle after the addition is complete, and allow the slurry to cool to about 22° C. Cool the slurry to about 5° C. and stir for about 2 hours. Filter the mixture and wash the cake three times with 500 mL cold ethanol. Dry the solid overnight in a vacuum oven at about 50° C. to provide 370 g (98% yield) of the title crystal form as a white solid.

Workup

  1. customequipped with overhead agitation
  2. temperatureheating mantle
  3. customto provide a homogeneous solution
  4. temperaturewhile maintaining the temperature above 72° C
  5. customThe salt may begin precipitating after approximately 380 mL of phosphoric acid solution
  6. additionis added
  7. customRemove the heating mantle
  8. additionafter the addition
  9. temperatureto cool to about 22° C
  10. temperatureCool the slurry to about 5° C.
  11. filtrationFilter the mixture
  12. washwash the cake three times with 500 mL cold ethanol
  13. customDry the solid overnight in a vacuum oven at about 50° C.

Sources & evidence

ORD record
ord-befc1f8f8d31425b8f0f88d33e5b5633
Source dataset
uspto-grants-2012_05
Patent number
US08188087B2

Linked notes

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