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Upstream product

• 69684-83-9 (+/-)-sorbinil 
• 67-63-0 isopropyl alcohol 

Relevant academic research and scientific papers

Process for the production of asymmetric hydantoins

An improved process for preparing (4S)-6-fluorospiro-[chroman-4,4''-imidazolidine]-2'',5''-dione (sorbinil) or its (2R)-methyl derivative (2-methylsorbinil) is disclosed herein, starting from p-fluorophenol in each instance. The final products obtained ha

Process for the production of an (S)-methyl or (S)-ethyl 4-amino-6-fluorochroman-4-carboxylate

An improved process for preparing (4S)-6-fluoro-spiro-[chroman-4,4''-imidazolidine]-2'',5''-dione (sorbinil) or its (2R)-methyl derivative (2-methylsorbinil) is disclosed herein, starting from p-fluorophenol in each instance. The final products obtained have known pharmaceutical value as agents for the control of certain chronic diabetic complications. Key steps concerned with the process involve converting p-fluorophenol into the appropriate β-(4-fluorophenoxy)alkane halide, followed by amidoalkylation with N-benzoyl or N-(lower alkanoyl)-α-hydroxyglycine to form an intermediate 2-amidoalkylated derivative thereof, and then dehydration and spiroalkylation of said intermediate by treatment with a dehydrating agent and a base to yield a spiroalkylated azlactone compound. The latter compound is then subsequently converted to the known 4-amino-6-fluorochroman-4-carboxylic acid or the novel (2R)-methyl derivative thereof, both in the form of their hydrohalide acid addition salts, by employing acid hydrolysis and the intermediate spiro-amino acid hydrohalide salt is thereafter converted to the corresponding methyl or ethyl ester and resolved with α-chymotrypsin to afford the desired (S)-methyl or (S)-ethyl ester. Treatment of either of these latter two esters with an alkali metal cyanate in an acid medium then effects conversion of same to the desired spiro-hydantoin ring compound. Alternatively, the spiro-amino acid hydrohalide salt can also be converted to the desired spiro-hydantoin ring compound in a known manner, involving a sequence of three reaction steps. The spiroalkylated azlactone compound of the instant invention, as well as the methyl and ethyl esters mentioned above, are themselves novel compounds and are valuable as synthetic intermediates in the process of this invention.

S-6-fluoro-4-aminochroman-4-carboxylic acid derivatives useful as intermediates for sorbinil

Chiral sorbinil intermediates of the formula STR1 wherein R is hydrogen or benzyloxycarbonyl and Y is hydroxy or amino, processes therefor, and processes for the conversion thereof to sorbinil.

Regeneration of 6-fluoro-4-chromanone from 6-fluoro-4-ureidochroman-4-carboxylic acid

6-Fluoro-4-chromanone can be regenerated from (R)-6-fluoro-4-ureidochroman-4-carboxylic acid, or from mixtures of (R)-6-fluoro-4-ureidochroman-4-carboxylic acid and its racemic modification, by oxidation with a permanganate, especially potassium permanganate. 6-Fluoro-4-chromanone is a chemical intermediate useful for preparing sorbinil, an aldose reductase inhibitor which can be used in clinical medicine for the control of the chronic complications of diabetes. (R)-6-Fluoro-4-ureidochroman-4-carboxylic acid and its racemic modification are by-products from the production of sorbinil from 6-fluoro-4-chromanone.

Regeneration of 6-fluoro-4-chromanone from by-products in the synthesis of sorbinil

6-Fluoro-4-chromanone, a sorbinil intermediate, is regenerated from enantiomeric and mixtures of enantiomeric and racemic compounds obtained as major by-products in the synthesis of sorbinil. The regenerated intermediate is useful in the synthesis of additional sorbinil.

Sorbinil by optical resolution of precursor 6-fluoro-4-ureidochroman-4-carboxylic acid

Sorbinil is obtained by cyclization of S-6-fluoro-4-ureidochromane-4-carboxylic acid, which is in turn obtained by resolution of racemic 6-fluoro-4-ureidochroman-4-carboxylic acid via diasteromeric salts with either D-(+)-(1-phenethyl)amine or L-(-)-ephedrine.