Carbon Dioxide → Ibuprofen, (+-)-

HRID 1914459Notes

Reaction equation

HRID 1914459 reaction equation
C(=O)=O.[OH:4][C:5]([CH:7]([C:9]1[CH:18]=[CH:17][C:12]([CH2:13][CH:14]([CH3:16])[CH3:15])=[CH:11][CH:10]=1)[CH3:8])=[O:6].CC(C)=O.O.C(=O)=O.N#N>CC(C)=O.O>[OH:6][C:5]([CH:7]([C:9]1[CH:10]=[CH:11][C:12]([CH2:13][CH:14]([CH3:15])[CH3:16])=[CH:17][CH:18]=1)[CH3:8])=[O:4]

Participants

5

Reactant 3

HCID 280Carbon Dioxide2×HCID 947NitrogenHCID 86660791HCID 86660791, compound

Product 1

HCID 3672Ibuprofen, (+-)-

Reagents, catalysts & solvents 1

HCID 18366337Propan-2-one--water (1/1)Solvent

Procedure

In a mixing reactor 7 of 300 mL capacity, 170 mL of a solution of the ibuprofen compound in acetone with a relative concentration to saturation of 63% and 90 mL of H2O, obtaining a suspension of the drug in the acetone-water mixture. Over this suspension CO2 is added with a volume of flow of 7 Kg/hr until the pressure P1 of reactor 7 reaches the 100 Bar. The temperature is kept constant throughout the entire process at 35° C. At these conditions, this system is formed by a transparent microemulsion consisting of the system ibuprofen/acetone/water/CO2. The microemulsion is left to stabilize at P1 and 35° C. during 15 minutes (see FIG. 2). The supply of CO2 is closed and the adding of N2 begins through the uppermost part of the reactor through valve 6, to maintain the pressure P1 constant at 100 bar within the reactor during the depressurization process of the microemulsion. The depressurization of the microemulsion from P1 to P2=1 bar, with the consequent rapid evaporation of CO2, is done through the opening of a valve 12. The evaporation of CO2 causes the water to again manifest its new anti-solvent characteristic over the dissolved ibuprofen in the organic phase, causing its precipitation. The precipitated particles are collected in filter 13 at P2=1 bar (atmospheric pressure). The precipitated particles are washed with CO2 at 40 Bar. The mother liquors are collected in container 15 through valve 14. The size of the particle of the ibuprofen compound was determined through a scanning electron microscope (SEM). The distribution of particle sizes of the collected solid phase in filter 13 have an average of 740 nm with a standard deviation of 100 nm. It was observed through X-ray powder diffraction that the particles obtained are crystalline, and by using the scanning electron microscope (SEM) that they have a homogenous spheroidal morphology (see FIG. 5A). The output of the process is of 86%.

Workup

  1. concentrationIn a mixing reactor 7 of 300 mL capacity, 170 mL of a solution of the ibuprofen compound in acetone with a relative concentration to saturation of 63% and 90 mL of H2O
  2. customobtaining
  3. customof reactor 7 reaches
  4. customis kept constant throughout the entire process at 35° C
  5. customAt these conditions, this system is formed by a transparent microemulsion
  6. waitThe microemulsion is left
  7. custombegins through the uppermost part of the reactor through valve
  8. temperature6, to maintain the pressure P1 constant at 100 bar within the reactor during the depressurization process of the microemulsion
  9. customThe depressurization of the microemulsion from P1 to P2=1 bar, with the consequent rapid evaporation of CO2
  10. customis done through the opening of a valve
  11. customThe evaporation of CO2
  12. customits precipitation
  13. customThe precipitated particles are collected
  14. filtrationin filter 13 at P2=1 bar (atmospheric pressure)
  15. washThe precipitated particles are washed with CO2 at 40 Bar
  16. customThe mother liquors are collected in container 15 through valve 14
  17. filtrationThe distribution of particle sizes of the collected solid phase in filter 13
  18. customobtained

Sources & evidence

ORD record
ord-0b63eeb598c240f8aaf1f814618f0718
Source dataset
uspto-grants-2013_12
Patent number
US08613953B2

Reaction notes

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