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Preparation of trans-fused 3,3a,8,12b-tetrahydro-2h-dibenzo[3,4:6,7]cycloh- epta[1,2-b]furan derivatives
   
Document Number
US Patent 6998494
Issued Date
February 14, 2006
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Abstract
The present invention concerns processes for the preparation of each of the 4 diastereomers of formula (I) ##STR00001## in stereochemically pure form from either of two enantiomerically pure precursors. The tetracyclic ringsystem having trans-fused five and seven membered rings is formed in an acid-catalysed cyclization reaction. The invention further relates to the thus obtained cis-fused tetracyclic alcohol intermediates, the methanamine end-products, the methanamine end-products for use as a medicine, in particular as CNS active medicines.
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Number of Claims:
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Published
February 14, 2006
Application Number
10/496,279
Filed
December 2, 2002
US Classification
549/457  
Int'l Classification
C07D   307/93   (20060101)  
Examiner
Priority Data
Dec 07, 2001 [EP] 01204961
USPTO Field of Search
549/457  
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7470809 - Process for the production of [2-(4-fluoro-benzyl)-phenyl]-acetic acid - Owned by Janssen Pharmaceutica N.V. (Beerse,BE)

The present invention relates to a novel process for the production of [2-(4-fluoro-benzyl)-phenyl]-acetic acid, a compound obtainable from phthalic anhydride. The process comprises the subsequent steps a) through e): a) reacting phthalic anhydride with fluorobenzene or a derivative thereof in appropriate reaction conditions; b) over reducing the product obtained in step a) at the ketone moiety; c) reducing the product obtained in step b) with sodium dihydro-bis(2-methoxyethoxy)aluminate (Red-Al) to the corresponding alcohol; d) chlorinating the alcohol obtained in step c); e) inserting CO into the product obtained in step d) through an appropriate Pd-containing catalytic system.In an alternative embodiment, the step e) is replaced by the steps f1) and f2): f1) reacting the product obtained in step d) with sodium cyanide; f2) hydrolysing the product obtained in step f1).The present invention provides a process for the production of [2-(4-fluoro-benzyl)-phenyl]-acetic acid which is suitable for industrial scale reactors (e.g. which is cleaner and more efficient). Also, [2-(4-fluoro-benzyl)-phenyl]-acetic acid is obtained as a crystalline material with a purity >95%.

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