Ketorolac → Ketorolac Tromethamine

HRID 636079

Reaction equation

HRID 636079 reaction equation
[CH:1]1[CH:2]=[CH:3][C:4]([C:7]([C:9]2[N:13]3[CH2:14][CH2:15][CH:16]([C:17]([OH:19])=[O:18])[C:12]3=[CH:11][CH:10]=2)=[O:8])=[CH:5][CH:6]=1.[NH2:20][C:21]([CH2:26][OH:27])([CH2:24][OH:25])[CH2:22][OH:23]>C(O)(C)C.O>[CH:1]1[CH:6]=[CH:5][C:4]([C:7]([C:9]2[N:13]3[CH2:14][CH2:15][CH:16]([C:17]([OH:19])=[O:18])[C:12]3=[CH:11][CH:10]=2)=[O:8])=[CH:3][CH:2]=1.[CH2:22]([OH:23])[C:21]([NH2:20])([CH2:26][OH:27])[CH2:24][OH:25]

Participants

5

Reactant 2

HCID 3826KetorolacHCID 6503Tris(hydroxymethyl)aminomethane

Product 1

HCID 84003Ketorolac Tromethamine

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 3776IsopropanolSolvent

Conditions

Temperature
40 °C

Procedure

Ketorolac acid (20 gm, Abbott Laboratories) was dissolved in 156.0 gm of isopropanol. A solution of 12.0 gm of tromethamine in 25.0 gm of water was added, and the mixture was heated to 40° C. to a solution. The solution was filtered thru a 0.2 micron filter. To the clear filtrate was added 356.0 gm of ethyl acetate, and the ternary solution was distilled under atmospheric conditions to approximately half the volume. Another aliquot of 356.0 gm of ethyl acetate was added and the mixture distilled to approximately half the volume. At this point solid started precipitating out. Ethyl acetate (356.0 gm) was added once more and the mixture distilled to approximately half the volume. The solution was cooled to 10° C. and the solid ketorolac tromethamine was isolated by filtration. The collected solids were dried under vacuum to afford 36.1 gm of the desired product. HPLC analysis showed a purity of >99% of the desired compound.

Workup

  1. filtrationThe solution was filtered thru a 0.2 micron
  2. filtrationfilter
  3. additionTo the clear filtrate was added 356.0 gm of ethyl acetate
  4. distillationthe ternary solution was distilled under atmospheric conditions to approximately half the volume
  5. additionAnother aliquot of 356.0 gm of ethyl acetate was added
  6. distillationthe mixture distilled to approximately half the volume
  7. customAt this point solid started precipitating out
  8. additionEthyl acetate (356.0 gm) was added once more
  9. distillationthe mixture distilled to approximately half the volume
  10. temperatureThe solution was cooled to 10° C.

Sources & evidence

ORD record
ord-bf293d6b9f3644d292de8c894de40e09
Source dataset
uspto-grants-2001_02
Patent number
US06191285B1

Linked notes

Loading…