Ketorolac → Ketorolac Tromethamine

HRID 636077

Reaction equation

HRID 636077 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>[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

4

Reactant 2

HCID 3826KetorolacHCID 6503Tris(hydroxymethyl)aminomethane

Product 1

HCID 84003Ketorolac Tromethamine

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Conditions

Temperature
10 °C

Procedure

Ketorolac acid (20 gm, Abbott Laboratories) was dissolved in 145 mL isopropanol. In a separate container, 10 gm of tromethamine (Aldrich Chemical Co.) was dissolved in 20 mL distilled water. The two mixtures were combined, mixed for 30 minutes then vacuum distilled under heat. Distillation was continued until approximately one half the volume remained, e.g., about 80 mL. Isopropanol (145 mL) was added and distillation continued until one half the volume remained, whereupon 270 mL of ethyl acetate was added and distillation of the ternary mixture continued. Upon removal of one-half the distillate, the ethyl acetate addition was repeated. When the volume was again brought to one half the starting volume, distillation was terminated. The solution was cooled to 10° C. and the solid ketorolac tromethamine isolated by filtration. The collected solids were dried under vacuum to afford 25 gm of the desired product. HPLC analysis showed purity of >99% of the desired compound.

Workup

  1. distillationdistilled water
  2. additionmixed for 30 minutes
  3. distillationvacuum distilled
  4. temperatureunder heat
  5. distillationDistillation
  6. additionIsopropanol (145 mL) was added
  7. distillationdistillation
  8. additionwas added
  9. distillationdistillation of the ternary mixture
  10. customUpon removal of one-half the distillate
  11. additionthe ethyl acetate addition
  12. distillationthe starting volume, distillation
  13. customwas terminated

Sources & evidence

ORD record
ord-a11c6095382e40e7944e16a4b855bfd3
Source dataset
uspto-grants-2001_02
Patent number
US06191285B1

Linked notes

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