Ethyl 2-chloropropionate, oxidation

Merck and Maeder have patented the manufacture of arecaidine by loss of water from l-methyl-4-hydroxypiperidine-3-carboxylic acid. A method of producing the latter has been describd by Mannich and Veit and has been developed by Ugriumov for the production of arecaidine and arecoline. With the same objective, Dankova, Sidorova and Preobrachenski use what is substantially McElvain s process,but start by converting ethylene oxide, via the chlorohydrin and the cyanohydrin, into -chloropropionic acid. The ethyl ester of this with methylamine in benzene at 140° furnishes methylbis(2-carbethoxyethyl) amine (I) which on refluxing with sodium or sodium Moamyloxide in xylene yields l-methyl-3-carbethoxy-4-piperidone (II). The latter is reduced by sodium amalgam in dilute hydrochloric acid at 0° to l-methyl-3-carbethoxy-4-hydroxypiperidine (III) which on dehydration, and hydrolysis, yields arecaidine (IV R = H), convertible by methylation into arecoline (IV R = CH3). 

This ester has been prepared by the action of ethyl jS-bromo-propionate on methylamine hydrochloride in the presence of silver oxide,1 by the addition of methylamine to ethyl acrylate,2 and by heating ethyl /3-chloropropionate, methylamine, and benzene in an autoclave.3... 

Alkylation, of 2-acetamidothiazoles, 35, 37 with alkali amides, 34, 35 of alkylaminothiazole, 34 with alcohols, 47, 80, 90 of aminothiazoles, with alcohols, 38 with benzyl chloride. 33 with chloracetic acid, 33 with chloracetic esters, 33 with 3-chloropropionic acid, 33 with dimethylaminoethylchloride, 35 with ethylene oxide, 34, 38 with ethyl iodide, 33 with phenethyl chloride, 35 with 2-propynyl bromide. 32 in aprotic solvents, 35 of azothiazoles, 105... 

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