Their use for the preparation of 70: glucokinase activators and production of cyclic ketal of ketone by Favorskii rearrangement

摘要

Susceptible to acid (acid-sensitive) ketones, in particular, a methodology for the acid-sensitive ketalized cyclic ketone to α- monohalogenation. One approach (for example, dimethylformamide (DMF)) include a halogen donor compound (eg, N- chlorosuccinimide) is reacted with a highly polar organic anhydrous reagents and ketone. As monohalogenated Another approach, that the reagent containing (methanol, ethanol, isopropanol and the like), an alcohol solvent, organic salts formed from carboxylic acids and amines catalyze the mono-halogenation of the ketal of the ketone was observed were. Monohalogenation is a rapidly even -5 ℃. Salts thereof, from the component containing a carboxylic acid amine and / or, without excessive degradation of the acid-sensitive ketal, can be allowed to form rapidly on the spot. Using iodosylbenzene, aryl ketone is one oxygenation. This methodology is applied to mono halogenation of acid-sensitive mono ketal ketone. Capacity to produce mono halide, an acid-sensitive ketones, to promote the synthesis using halogenated acid sensitivity ketone. As an example of the corresponding, easy synthesis of halogenated acid-sensitive ketones, S- ketal useful as intermediates in the preparation of the glucokinase activator - a new approach to synthesize acid S-MBA the (S- methylbenzylamine) provide. Cyclic ketal of the ketone as an overview of this scheme, the mono-halogenated, using monohalogenated methodology of the present invention, is manufactured. Then, under conditions that provide the racemic acid counterpart of chiral salt of the desired halogenated compound is subjected to a Favorskii rearrangement. From the racemic mixture, chiral salt of the desired, be easily recovered in enantiomerically pure form.