Ammonia → 3-Cyano-3-(3,4-dichlorophenyl)propionic acid

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Reaction Steps

3-Cyano-3-(3,4-dichlorophenyl)propionic acid (III) is prepared by reacting sodium chloroacetate with 3,4-dichlorophenylacetonitrile (II), for example in liquid ammonia in the presence of sodium amide according to the technique of A. G. CHIGAREV and D. V. IOFFE, Zh. Org. Khim. 3, 85-8 (1967), or in the presence of another very strong base such as sodium or potassium tert-butylate in liquid ammonia at -33° C. or in anhydrous dimethyl sulfoxide at room temperature. The yield of 3-cyano-3-(3,4-dichlorophenyl)propionic acid isolated is 74 to 78%, but it is even better if the product is not isolated, because it suffices to react it with D-(-)-N-methylglucamine, an inexpensive industrial product obtained from D-glucose and methylamine (KARRER, HERKENRATH--Helv. Chim. Acta, 20, 37 (1937)), in order to crystallize all the racemic cyanoacid (III) in the form of the salt of the levorotatory acid. The yield is excellent, being 190% based on the levorotatory enantiomer contained in the racemate (III). The crystallization solvent can be methanol, ethanol, Cellosolve® or any other suitable solvent. The resolution temperature is between the boiling point of the solvent and 0° C. The N-methylglucamine must be present in at least the stoichiometric amount. It is preferably used in slight excess.

Provenance & Evidence