Making of N-methyl tryptamine

United States Patent: 4946840

Preparation of 1-methyl tryptamine

This step began with a solution of:

(1) 1.6 g (10 mmol) of tryptamine; and (2) 20 ml of dimethylformamide. This solution was added dropwise to a suspension of: (1) 440 mg (11 mmol) of sodium hydride oil in (2) 30 ml of dimethylformamide. A dark brown solution resulted.

The dark brown solution was then stirred for 30 minutes at room temperature, cooled to 0.degree. C., and mixed with methyl iodide. (The methyl iodide was purified before use by passing it through a column of basic alumina.) After stirring for an hour at room temperature, the reaction mixture was partitioned between ethyl acetate and water. The ethyl acetate layer was washed with saturated brine and then dried by sodium sulfate filtration. The filtrate was concentrated, the filtration residue loaded onto a 5.times.25 cm silicon dioxide column, and the column eluted with dichloromethane:methanol:triethylamine, 95:4:1. Pure fractions were concentrated to afford 970 mg (a 56% yield) of the first intermediate as a yellow oil.

note:
1. usual procedure requires protection of NH2 then alkylation on the indole Nitrogen which is unnecessary if you follow the above procedure.
the reaction works fine although the yield is not high and product separation is difficult.