Trimethoxy-methylphenethylamine

5-Trimethoxyphenylacetone (25.0 g.— 0.111 mole), hydroxy-lamine hydrochloride (9.3g.—0.134 mole) and potassium acetate (15.6g.— 158 mole) were added to 400 mL. of 70% ethyl alcohol contained in a liter flask fitted with a reflux condenser. The mixture was heated on a steam bath to gentle reflux for 3-1/2 hours. The cooled reaction mixture was evaporated to dryness under reduced pressure and the residue extracted four times with 150 mL. portions of benzene. The combined benzene extracts were washed twice with 75 mL. portions of water and then dried over a anhydrous MgS04. Evaporation of the benzene under reduced pressure left a tan oil (26.8 g.), which was redissolved in benzene and diluted by dropwise addition of petroleum ether until white crystals appeared. After completion of the crystallization, filtration yielded 20.1 g. m.p. 80—85°C. Recrystallization from benzene-petroleum ether yielded 18.1 g. white crystals—m.p. 91.5—93°C. 

The reaction mixture was filtered to remove the catalyst and the solvent evaporated under reduced pressure to leave a dark yellow residue. The residual oil was dissolved in excess ether and sufficient 4 N alcoholic hydrochloric acid added to precipitate the hydrochloride of the product. The amine hydrochloride was filtered and washed with ether. It weighed 17.5 and melted at 178—181° C. Recrystallization from isopropyl alcohol yielded 14.9 g. of white crystals—m.p. 186.5—187.2° C. 

A mixture of 36.2 g. of 3,4-dihydroxybenzyl methyl ketone oxime. 3.7 g. of platinum oxide, 19.5 mL. of concentrated hydrochloric acid and 750 mL. of butanol is hydrogenated at room temperature until no more hydrogen is absorbed. The mixture is made neutral by the addition of sodium bicarbonate, and about 150 g. of sodium sulphate are added and the mixture is filtered. To the filtrate, a solution of 11.5 g. of succinic-acid in 100 mL. of butanol are added, the solution is concentrated to a volume of about 100 mL. and cooled. The succinate of 1-(3,4-dihydroxy-phenyl)-2-hydroxaminopropane precipitates and is collected and dried. Yield 27 g., m.p. 157—159°C. 

From the succinate the free hydroxamino compound can be obtained by treatment with aqueous sodium bicarbonate, extraction with diethyl ether and evaporation to dryness of the solvent. The product has m.p. 120—123°C. 

Into a mixture of 180 g. of l-(3,4-dihydroxyphenyl)-2-nitroproplene, 1000 mL. of methanol, 750 mL. of water and 300 mL. of about 12% aqueous hydrochloric acid, in the presence of 18 g. of 19% palladium on charcoal, hydrogen is bubbled until absorption, practically ceases. The mixture is filtered and the filtrate is concentrated to a volume of about 1000 mL. and extracted with ethyl acetate. On evaporation of the solvent, 131 g. (78%) of 3,4-dihydroxybenzyl methyl ketone oxime are obtained, with m.p. 145—148°C. Source Lepett 1967 

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Synonyms 3,4,5-Trimethoxy-a methylbenzeneethanamine 3,4,5-trimethoxy-a-methylphenethylamine 3,4,5-TMA Trade names ... 

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