Hydantoic acid → Phenylpropanolamine

참여 물질

반응 단계

Later developments in the overall method of production then finally gave a process for producing sorbinil which involved the following steps, viz., (1) p-fluorophenol was first converted to β-(p-fluorophenoxy)propionitrile by treatment with acrylonitrile in the presence of Triton B; (2) the nitrile intermediate was then converted to β-(p-fluorophenoxy)propionic acid by means of hydrochloric acid; (3) β-(p-fluorophenoxy)propionic acid was then condensed in the presence of concentrated sulfuric acid at 50° C. to afford 6-fluoro-4-chromanone; (4) the latter compound was thereafter condensed with potassium cyanide and ammonium carbonate in ethanol under standard Bucherer-Berg conditions to give the racemic precursor of sorbinil, which is called dl-6-fluoro-spiro-[chroman-4,4'-imidazolidine]-2',5'-dione; (5) the latter racemic spiro-hydantoin was then hydrolyzed with aqueous sodium hydroxide to the corresponding spiro-amino acid, which is called 4-amino-6-fluorochroman-4-carboxylic acid; (6) the latter acid, which can not be conveniently isolated in the process, was then treated in situ with sodium or potassium cyanate (after first adjusting the pH of the aqueous solution) in order to convert the amino acid to the corresponding hydantoic acid, which is called 6-fluoro-4-ureidochroman-4-carboxylic acid; (7) the latter hydantoic acid was then resolved according to the method described by B. W. Cue, Jr. et al. U.S. Pat. No. 4,435,578 by treatment with l-(-)-ephedrine in aqueous methanol to form the l-(-)-ephedrine salt of (4S)-6-fluoro-4-ureidochroman-4-carboxylic acid; and (8) the latter crystalline salt was thereafter converted to sorbinil by heating the diastereoisomer in glacial acetic acid to effect conversion to the desired (4S)-6-fluoro-spiro-[chroman-4,4'-imidazolidine]-2',5'-dione.

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