Formaldehyde → 3-{N-[2-(chroman-3-yl)ethyl]-N-methylamino}-propionic acid methyl ester

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Reaction Steps

3.0 g (0.01 mol) of 3-{N-[2-(chroman-3-yl)ethyl]amino}propionic acid methyl ester hydrochloride are suspended with stirring in 30 ml of acetonitrile, and 4.0 ml (0.05 mol) of 37% formaldehyde in water are added thereto. 0.84 g (0.01 mol) of sodium hydrogen carbonate is then added and stirring is continued, yielding a clear solution. 1.0 g of sodium cyanoborohydride is added in portions to the solution and the pH of the suspension is then adjusted to 7 by the dropwise addition of glacial acetic acid. The reaction mixture is then stirred for 1 hour at room temperature, the solvent is distilled off under reduced pressure and the oily residue is partitioned between 50 ml of diethyl ether and 15 ml of N sodium hydrogen carbonate solution. The organic phase is separated off, dried over sodium sulfate and concentrated by evaporation. Purification by chromatography on a silica gel column (diameter 2 cm, length 30 cm, Kieselgel® Merck 60) with toluene/ethanol (9:1 parts by volume) yields 3-{N-[2-(chroman-3-yl)ethyl]-N-methylamino}-propionic acid methyl ester in the form of an oil. 3-{N-[2-(chroman-3-yl)ethyl]-N-methylamino}-propionic acid hydrochloride having a melting point of 169°-170° is obtained from the latter in a manner analogous to that described in Example 1 by heating with 20 ml of 4N hydrochloric acid.

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