To a mixture of 24.1 g N-methylformanilide and 27.3 g POCl₃ that had been allowed to stand at room temperature until strongly red-colored (about 0.5 h) there was added 13.8 g solid 2,5-diethoxyanisole and the mixture was heated on the steam bath for 2 h. The black, thick reaction product was poured over chipped ice and, with continuous stirring, the color lightened and there was the formation of a yellowish powder. After a few h standing, this was removed by filtration and sucked as dry as possible. The 32 g of damp product showed the presence of isomeric contaminatiion by GC, and the aqueous mother liquor, upon extraction with CH₂Cl₂ and concentration, showed yet more aldehyde-like impurities. The isolated solids were recrystallized from 125 mL boiling MeOH giving 15.8 g yellowish crystals (wet weight) that still showed detectable impurities by GC. A second recrystallization from 100 mL boiling MeOH gave off-white fluffy crystals of 2,5-diethoxy-4-methoxybenzaldehyde which weighed, after air drying, 8.5 g. The mp was 109–110 °C. The combined mother liquors from the two MeOH crystallizations were stripped of solvent, and the resulting solid mass crystallized again from MeOH to give a second crop of aldehyde, 5.7 g, with a mp of 110–111 °C. A solution of 1.0 g of this aldehyde and 0.7 g malononitrile in 40 mL warm absolute EtOH was treated with a few drops of triethylamine. In a minute or so, there was the formation of crystals. These were removed by filtration, washed with EtOH, and air dried, giving 0.6 g of 2,5-diethoxy-4-methoxybenzalmalononitrile as brilliant yellow crystals with a mp of 156.5–158 °C.

A solution of 6.7 g 2,5-diethoxy-4-methoxybenzaldehyde in 21 g glacial acetic acid was treated with 3.1 g nitroethane and 1.93 g anhydrous ammonium acetate, and heated on the steam bath for 2.5 h. The addition of a small amount of H₂O to the hot reaction mixture instituted crystallization of an orange product which, after the mixture had come to room temperature and stood for several h, was removed by filtration, H₂O washed, and air dried. The product, 1-(2,5-diethoxy-4-methoxyphenyl)-2-nitropropene, was dull orange in color, weighed 3.0 g and had a mp of 84–86 °C. An analytical sample from toluene had a mp of 85–86 °C. Anal. (C₁₄H₁₉NO₅) C,H.

To a gently refluxing suspension of 2.0 g LAH in 250 mL anhydrous Et₂O under a He atmosphere, there was added 2.8 g 1-(2,5-diethoxy-4-methoxyphenyl)-2-nitropropene by allowing the condensing Et₂O to drip into a shunted Soxhlet thimble containing the nitrostyrene. This effectively added a warm saturated solution of the nitrostyrene dropwise. The addition took 1 h and the refluxing was continued for an additional 6 h. The reaction mixture was brought down to ice-bath temperature, and the excess hydride was destroyed by the cautious addition of 150 mL 1.5 N H₂SO₄. When the aqueous and Et₂O layers were finally clear, they were separated and 50 g of potassium sodium tartrate were dissolved in the aqueous fraction. Aqueous NaOH was then added until the pH was >9, and this was then extracted with 3×150 mL CH₂Cl₂. Removal of the solvent under vacuum produced 2.3 g of a clear white oil that was dissolved in 300 mL anhydrous Et₂O and saturated with anhydrous HCl gas. At first the solution remained completely clear, and finally there was the start of the formation of fine white crystals. When the crystallization was complete, these solids were removed by filtration, Et₂O washed, and air dried. There was thus obtained 2.2 g of 2,5-diethoxy-4-methoxyamphetamine hydrochloride (EME) with a mp of 162–164 °C with prior softening at 154 °C. Anal. (C₁₄H₂₄ClNO₃) C,H,N.