Study On Process Of L-ascorbyl Ibuprofenate

An environmentally benign process has been established for the preparation of ibuprofenmethyl ester, with methanol and ibuprofen as reactants, p-toluene sulfonic acid (PTSA) ascatalyst, and glycerol as adsorbent of water and the solvent of catalyst. The immiscibility ofibuprofen methyl ester and glycerol was exploited in this process. The reaction conditionshave been optimized. At the optimized condition, the conversion rate can be reached at97.10%. The simulated moving bed (SMB) chromatography was used to isolate the products,55~60mesh silica gel was used as a stationary phase, dichloromethane as mobile phase/eluent.The roduction capacity was353.4Kg/d. The yield greater than95%. Detected by LC/MS, thepurity of ibuprofen methyl ester was99.9%. For whole the process, there is no effluent needto be discharged, neither the synthesis, nor the purification.The specificity of the lipase for direct esterification or transesterification was studied. Theresult shows transesterification prevailled over direct esterification when ibuprofen methylester was used as an acyl donor, leading to ascorbyl ester of ibuprofen. The transesterificationreaction didn’t produce water which was difficult to remove. The reaction conditions havebeen optimized. The effect of methanol removal by reduced pressure on the reactionequilibrium was studied. Ester production was strongly promoted by reduced pressure, due tomethanol elimination under0.035-0.040MPa. The conversion rate increased from5.06%to16.06%. The conditions of reaction has been determined as follows: ibuprofen methyl ester ashydrophobic substrate-acyl donor, Novozyme435as catalyst, tert-butyl alcohol as solvent.An new purification process has been established for the preparation of L-ascorbylIbuprofenate. Unreacted ibuprofen methyl ester had been detach from the reaction mixturewith dichloromethane. The simulated moving bed (SMB) chromatography was used to isolatethe products,100~200mesh silica gel was used as stationary phase, methanol/dichloromethane (1:1, v/v) as mobile phase/eluent. The roduction capacity was9.3Kg/d. Therecovery rate was greater than90%, the chromatographically pure compound was obtained,total yield was greater than13.5%. It is an environmentally process, preparation of high purityproducts without water, and avoided the waste of L-ascorbic acid raw materials and thecontamination of pharmaceutical.