Patent GB828521
Abstract: 2-(b-Aminoethyl)-indole (isotryptamine) is prepared by reducing an indole-2-carboxylic acid dialkylamide (e.g. the dimethylamide, obtained from the acid chloride and dimethylamine) with lithium aluminium hydride to a 2-dialkylaminomethyl indole, quaternizing the latter with a methyl halide or dimethyl sulphate, reacting the quaternary ammonium compound with an alkali metal cyanide to form indolyl-(2)-acetonitrile, and hydrogenating or reducing the latter to isotryptamine. Salts, e.g. the hydrochloride, may be prepared.
Details:a) 31 g of indole-2-carboxylic acid are suspended in 500 ccm of abs benzene and 50 ccm of thionyl chloride in 50 ccm of abs. benzene are added dropwise, while introducing nitrogen, within half an hour on completion of the dropwise addition, the whole is heated to 45 for 1 hours, after which time a complete solution should be obtained.
The benzene solution is concentrated to one third of its volume in vacuum and the residue is poured into a solution of 23 g of dimethylamine in 230 ccm of benzene which has been cooled with ice After half an hour, water is added and the reaction product which precipitates is filtered off under suction The indole-2-carboxylic acid dimethylamide is recrystallised from a great deal of alcohol M P. 180-182.
b) 25 g of lithium aluminium hydride are dissolved in 500 ccm of abs tetrahydrofurane and a solution of 52 g of indole-2-carboxylic acid dimethylamide in 500 ccm of tetrahydro2 828,521 furane is added dropwise The whole is kept for 5 hours at 45 while stirring well, then cooled to -10 and carefully decomposed with water It is filtered under suction and the solvent is distilled off The residue is taken up in ether, the ethereal solution is washed with water, dried and concentrated whereupon the residue is distilled in a high vacuum The 2-dimethylaminomethyl indole passes over at 118-120 under 0,3 mm pressure.
c) 52,2 g of 2-dimethylaminomethyl indole are dissolved in 150 ccm of abs ethyl acetate and 43 g of methyl iodide are carefully added dropwise The 2-trimethylammoniomethyl indole iodide crystallises out It is filtered off under suction, washed with ethyl acetate and dried M P 160.
d) 94 g of the above quaternary salt are refiuxed for 18 hours while introducing nitrogen in 58 g of potassium cyanide in 2 4 litres of abs methanol Two thirds of the methanol are then distilled off and the residue is poured into water The mixture is thoroughly extracted with ether, the ether extract is washed with diluted hydrochloric acid, dried and concentrated On adding ether, the indolyl( 2)-acetonitrile crystallises M P 96-97 .
e) 50 g of the above nitrile are dissolved in 200 ccm of abs alcohol saturated with ammonia and hydrogenated in the presence of g Raney nickel at 80-90 under an excess hydrogen pressure of 120 atm The calculated amount of hydrogen is taken up within 45 minutes The catalyst is filtered off and the alcohol is evaporated off in vacuum On adding ether, the residue crystallises The 2-(b)-aminoethyl)-indole melts at 101-102.
The hydrochloride melts at 220 celsius.
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See also:
Post 436968 (not existing)
