Methodology for the manufacturable synthesis of valproic acid conjugates

•Valproic acid assay design difficult: small size, no UV activity, one acid group.•Aminomethylvalproic acid is generally useful for preparing other conjugates.•The conjugate synthesis used low cost reagents/conditions and was reproducible.•This valproic acid conjugate was used to develop a chemilluminescent immunoassay. An efficient synthesis of a chemiluminescent valproic acid conjugate is described. Reaction of diethyl propylmalonate with 4-bromobutylphthalimide produced an amino protected malonate, which was deprotected with hydrazine and treated with HCl to produce an aminoderivatized valproic acid. Reaction with an acridinium active ester produced the conjugate in good yield. Careful selection of commercially available materials and mild conditions made this pathway amenable to scale up. This strategy offers a general method for the preparation of valproic acid conjugates.