Patent ID: 6689904
Filing Date: 2004-02-10
Classification: A61P,C07C,C07D

Abstract:
A process for preparation of a bridged tricyclic compound of the formulae: wherein X is (CH2)n, O, S, SO, SO2 or CR1R2; n is 1 or 2; R1 and R2 are, independently, hydrogen, halogen, hydroxy, alkyl of one to six carbon atoms, alkoxy of one to six carbon atoms, or R1 and R2, taken together with the carbon to which they are attached, form cycloalkyl of three to six carbon atoms, an alkylidene of up to six carbon atoms or a carbonyl; the process comprising the steps of: a) treating keto-acid of formula (1): â€ƒin the presence of ammonium carbonate and an alkali metal cyanide in a volume of organic solvent/water to give a spiro-fused hydantoin as a mixture of diastereomers having the formula (2); b) treating the spiro-fused hydantoin mixture of diastereomers (2) with an appropriate benzylic halogenide or sulfonate and alkali metal carbonate in an aprotic solvent to provide tri-substituted diastereomeric mixture of hydantoins (3); â€ƒwherein R represents the benzyl residue of the corresponding benzylic halogenide or sulfonate; c) separating the exo- and endo-racemic pairs of tri-substituted diastereomeric mixture of hydantoins (3) to yield the racemic mixture of (4) and (4â€²); d) resolving the racemic mixture of (4) and (4â€²) on a chiral column to produce both enantiomers (4) and (4â€²) in an enantiomerically pure form; e) treating intermediates (4), (4â€²), or a mixture thereof, with base to provide enantiomers of the formulae (5) and (5â€²): f) treating the compounds (5) and (5â€²) with a palladium on carbon catalyst to provide the dextro-(+) and levorotatory (âˆ’) forms of the compounds (6â€²) and (6).