4437-01-8

m-PEG7-alcohol is a PEG linker containing a hydroxyl group. The hydroxyl group enables further derivatization or replacement with other reactive functional groups. The hydrophilic PEG spacer increases solubility in aqueous media.

The presence of heptaethylene glycol monomethyl ether (HGME) as a process impurity and degradation impurity in the final purified form of Benzonatate is a determining factor in establishing the safety, identity, strength, purity, and quality of the drug substance. Owing to the cutaneous toxicity of HGME in the BNZ drug substance, a suitable and selective analysis method is required for its quantitation[1].

reagent type: cross-linking reagent

A 60% NaH dispersion in mineral oil was added in batches to a stirred solution of triacetylene glycol (35.7 mmol) in anhydrous DMF (25.7 mL) under nitrogen protection, and the mixture was stirred for 1 hour at room temperature. Subsequently, a solution of 2-(2-(2-methoxyethoxy)ethoxy)ethyl methanesulfonate (23.36 mmol) in anhydrous DMF (4 mL) was added in a single addition to the resulting salt, and stirring was continued for 3.5 hours at room temperature. The progress of the reaction was monitored by thin layer chromatography (TLC with 12% unfolding agent ratio). Upon completion of the reaction, the reaction mixture was diluted with an equal volume of 1N HCl, extracted with ethyl acetate (2 x 20 mL) and the organic phase discarded. The aqueous phase was extracted and post-treated to give heptaglycol monomethyl ether in 82-84% yield.

PEGs

[1] Lakshmi Narasimha Rao Katakam, Vishnu Murthy Marisetti, Santhosh Kumar Ettaboina. “Development and validation of LC–MS method for the determination of heptaethylene glycol monomethyl ether in benzonatate bulk drugs.” Biomedical Chromatography 35 7 (2021).