The synthesis of mephedrone, mentioned as ‘toluyl-alpha-monomethyl-aminoethylcetone’, was first described in 1929 by Saem de Burnaga Sanchez. The most straightforward route of synthesis for mephedrone is by reacting the suitably substituted bromopropiophenone with methylamine; the resulting product is always racemic. Therefore, mephedrone is most likely synthesised by bromination of 4-methylpropiophenone (1-(4-methylphenyl)-1-propanone) followed by reaction of the resulting 4-methylbromopropiophenone (1-(4-methylphenyl)-2-bromo-1-propanone) with an excess of methylamine or methylamine hydrochloride and an acid scavenger. The reaction is then quenched with gaseous or aqueous hydrochloride providing the hydrochloride salt that needs to be recrystallised. This is a relatively straightforward option because the starting materials are often commercially available or easily synthesised. This requires similar equipment and chemical knowledge to that needed for the synthesis of, for example, amphetamine or MDMA. The main precursor of mephedrone, 4-methylpropiophenone, is commercially available on the Internet.

There is the potential that if the substituted ephedrine analogue (4-methylephedrine) is available, then its oxidation with, for example, potassium permanganate or potassium dichromate is also a feasible method that does not require a professional laboratory. There is no
evidence that this is currently occurring in Europe. This method, similar to the one used for the clandestine synthesis of methcathinone, requires reacting the precursor with a solution of potassium permanganate in diluted sulphuric acid. The precursor can be obtained in a specific enantiomeric form, ensuring that the synthesis is stereoselective. One of the possible hazards of the permanganate process could be that users can suffer manganese poisoning if the product is not purified.

However, analysis of seized and purchased mephedrone has shown that it is generally of high purity (>95 %). There is limited evidence that precursors used in the manufacture of mephedrone are found in the final product.

Alternative synthetic methods, though more cumbersome, have been described in the literature such as the Hartung-Munch procedure. More synthetic routes for mephedrone may exist.

Reports from at least four Member States indicated legal production and distribution from Asia and in particular from China and bordering countries in South-East Asia. Final packaging of mephedrone, prior to sale, seems to be carried out by European suppliers. There have also been seizures of tableting machines used for mephedrone processing in Europe, indicating that the drug has also been prepared for sale on the illicit market.