GB770277A - Amino-propanediols and their derivatives - Google Patents

Abstract

The invention comprises compounds of the formula <FORM:0770277/IV(b)/1> and the synthesis thereof from p-methylsulphonyl-acetophenone by the following steps: the ketone is halogenated to give a p-methylsulphonyl-phenacyl halide which is treated with hexamethylene tetramine to form a complex thereof; hydrolysis of the latter with mineral acid yields a salt of p-methylsulphonyl-a -aminoacetophenone which is then N-acylated; the product is condensed with formaldehyde (in the presence of an alkaline catalyst) to give p-methylsulphonyl - a - acylamido - b - hydroxy - propiophenone and the keto group then reduced; if the N-acyl group is not dichloracetyl the product is hydrolysed to 1-(p-methylsulphonyl - phenyl) - 2 - aminopropane - 1 : 3 - diol and the latter re-acylated with a dichloracetylating agent. Optical resolution may be carried out at the amino-diol stage by the formation of a salt with an optically active acid, or alternatively the N-dichloracetyl compound is esterified with succinic anhydride (in the presence of an organic base), the product resolved by means of its strychnine salt, the optically active salts converted to the free acids and the succinyl group hydrolysed off; the last step is preferably carried out with an aqueous solution of a strong alkali containing a water-miscible organic solvent at -20 DEG to +50 DEG C. The preferred products are the threo isomers. The step of reducing the ketone to the secondary alcohol may be effected with nascent hydrogen (metal and acid, water or alcohol) or with an aluminium alkoxide. The N-dichloracetylation may be brought about by a dichloracetic ester, halide or anhydride, or by chloral cyanhydrin in the presence of alkali. Examples show the production of the following compounds: p-methylsulphonyl-phenacyl bromide and its hexamethylene tetramine complex, p - methylsulphonyl - a - amino - acetophenone hydrochloride, p-methylsulphonyl-a -acetamido-acetophenone, p - methylsulphonyl - a - acetamido - b - hydroxypropiophenone (dl-form), 1-(p - methylsulphonyl - phenyl) - 2 - acetamidopropane -1 : 3-diol (dl-threo form), 1-(p-methylsulphonyl - phenyl) - 2 - aminopropane - 1 : 3 - diol (dl-threo form, resolved via camphorsulphonate), 1-(p-methylsulphonyl-phenyl)-2-dichloracetamidopropane - 1 : 3 - diol (dl - threo form; l-threo form made by resolution of strychnine salt of 3-succinic ester and also by direct N-acylation of l-form of amino-diol), p-methylsulphonyl - a - dichloracetamido - acetophenone, p - methylsulphonyl - a - dichloracetamido - b - hydroxypropiophenone (dl-form), p - methylsulphonyl - a - carbethoxyamino - acetophenone, p - methylsulphonyl - a - carbethoxyamino - b - hydroxypropiophenone (dl-form) and 1-(p-methylsulphonyl-phenyl)-2-carbethoxyaminopropan - 1 : 3 - diol (dl-threo form). Reference has been directed by the Comptroller to Specifications 726,495, 745,900 and 746,016.