SYNTHESIS: To a solution of 20.9 g methoxyamine hydrochloride in 75 mL MeOH (a strongly acidic solution) there was added 4.45 g 3,4-methylenedioxyphenylacetone (see under for its preparation) followed by 1.10 g sodium cyanoborohydride. There was the immediate formation of a solid phase, and the evolution of what appeared to be hydrogen cyanide. To this there were added about 4 mL 5% NaOH which brought the pH to the vicinity of 3 or 4. Another 1.0 g of sodium cyanoborohydride was added (no gas evolution this time) and stirring was continued at ambient temperature for 6 days. All was added to 500 mL H₂O, acidified with 10 mL HCl, and extraction with 3×100 mL CH₂Cl₂ removed almost all the color. The aqueous phase was made basic with 25% NaOH, and extracted with 4×100 mL CH₂Cl₂. Evaporation of the solvent from these extracts yielded 1.8 g of a pale yellow oil which, on distillation at 90–95 °C at 0.5 mm/Hg, gave a 1.6 g fraction of an absolutely white, viscous, clear oil. This was dissolved in 8 mL IPA and neutralized with concentrated HCl. The product was an exceptionally weak base, and appropriate end points must be respected on the external pH paper (yellow to red, rather than purple to orange). Anhydrous Et₂O was added to the point of turbidity, and as soon as crystallization had actually started, more Et₂O was added with stirring, for a net total of 200 mL. After a couple of h standing, the fine white crystalline 3,4-methylenedioxy-N-methoxyamphetamine hydrochloride (MDMEO) was removed by filtration, Et₂O washed, and air dried to constant weight. There was obtained 1.7 g of a product with a mp of 143–146 °C. The proton NMR was excellent with the N-methoxyl group a sharp singlet at 4.06 ppm. Anal. (C₁₁H₁₆ClNO₃) N.

DOSAGE: greater than 180 mgs.

DURATION: unknown

EXTENSIONS AND COMMENTARY: Why the interest in the N-methoxy analogue of ? There are several reasons. One, this is an isostere of and it would be interesting to see if it might serve as a primer to the promotion of the effectiveness of other drugs (see primer discussion under ). In one experiment, wherein a 60 microgram dosage of was used an hour and a half after a 180 milligram load of MDMEO, there was no augmentation of effects. Thus, it would appear not to be a primer. Another reason for interest was that the material, although having an extremely similar overall structure to most of the active MD-series compounds, is very much a weaker base. And , which is also a very much weaker base than MDA, still shows the action and potency of MDA. And, as this compound appears to be inactive, base strength is not a sole predictor of activity.