Novel resolution process for racemic spiro-hydantoins

Organic compounds -- part of the class 532-570 series – Organic compounds – Heterocyclic carbon compounds containing a hetero ring...

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548308, 548309, C07D21538, C07D49110

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active

049526944

ABSTRACT:
A novel three-step process for resolving a racemic spiro-hydantoin compound into its optical antipodes is disclosed, which involves (1) reacting said racemic compound with an optically-active asymmetric isocyanate of the formula RNCO, wherein R is (S)- or (R)-1-phenylethyl or (S) or (R)-1-(1-naphthyl)ethyl, to form the corresponding diastereomeric uredio compound; (2) separating the resulting diastereomeric mixture into its component parts, and (3) thereafter converting the separated ureido diastereomers obtained in step (b) to the corresponding asymmetric hydantoin compounds by treatment with an alkali metal lower alkoxide (C.sub.1 -C.sub.4), followed by acidification, whereupon the desired optical isomer is obtained. The final products so obtained, such as (4S)-(+)-6-fluoro-2,3-dihydro-spiro[4H-1-benzopyran-4,4'-imidazolidine]-2' , 5'-dione (sorbinil) and (5'S)-3'-chloro-5', 6', 7', 8'-tetra-hydro-spiro[imidazolidine-4,5'-quinoline]-2,5-dione, are known to be useful in preventing or alleviating certain chronic diabetic complications. The aforementioned diastereomeric uredio intermediates are novel compounds.

REFERENCES:
patent: 4117230 (1978-09-01), Sarges
patent: 4130714 (1978-12-01), Sarges
patent: 4716113 (1987-12-01), Urban
Reinhard Sarges et al., in the Journal of Organic Chemistry, vol. 47, p. 4081 (1982).
William H. Pirkle et al., in the Journal of Organic Chemistry, vol. 49, p. 2433 (1984).
The Merck Index, 1426, Merck & Co., Inc., Rahway, NJ (1983).

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