Identification of impurities in the production of terbinafine hydrochloride

Abstract

The purity of the parent substance of (E )-N-(6,6-dimethylhept-2-en-4-ynyl)-N-methylnaphth-1-ylmethylamine (terbinafine) is evaluated via TLC identification of the main impurities appearing during its synthesis via alkylation of N-methylnaphth-1-ylmethylamine with 1-chloro-6,6-dimethyl-2-hept-2-en-4-yne The possible formation of impurities including N

Programmed Sequential Additions to Halogenated Mucononitriles

“…All diastereomeric ratios were determined by 1 H NMR analysis of an aliquot from the crude reaction mixture. Yields refer to isolated yields of compounds estimated to be ≥ 95% pure as determined by 1 H NMR analysis unless otherwise noted.…”

“…The solution was cooled to room temperature, placed on ice, and quenched with cold aqueous saturated sodium bicarbonate (ca 12 mL, until bubbling subsided). The mixture was extracted with ethyl acetate (3 x 2 mL), dried over Na2SO4, filtered and concentrated to give off-white/yellow solid, which was analyzed by 1 H NMR. The title compound was synthesized via the general chlorination procedure A described above using 1,3-dichloro-5,5-dimethylhydantoin (0.197 g, 1.00 mmol, 2.00 equiv).…”

“…This procedure afforded 42.6 mg (86%) of the title compound as an orange solid. The compound was obtained as a 10:1 mixture of diastereomers as judged by 1 (41.4 mg, 200 µmol, 1.00 equiv). Tetrakis(triphenylphosphine)palladium(0) (16.2 mg, 14.0 µmol, 7.00 mol%) and copper (I) iodide (4.60 mg, 24.0 µmol, 12.0 mol%) were added followed by dioxane (2.0 mL, 0.10 M).…”

“…The synthesis of dimeric natural products primarily relies on coupling two similarly sized monomers and often leverages the inherent symmetry of the compound. 1,2 These strategies are efficient but require ready access to the requisite monomer. Moreover, additional postfunctionalization of the monomer is often necessary to access heterodimeric (or unsymmetrical homodimeric) substrates.…”

“…Thus, we began our studies by evaluating the efficacy of various chlorinating reagents to react with 4. 24 Common chlorinating reagents as Nchlorosuccinimide and bleach provided monochlorination products in low yield by 1 H NMR analysis of the crude reaction mixture. Reagents such as Palau'chlor, 25 and iodobenzene dichloride were also ineffective for this transformation.…”