135139-01-4Relevant academic research and scientific papers
Process research on the asymmetric hydrogenation of a benzophenone for developing the manufacturing process of the squalene synthase inhibitor TAK-475
Goto, Mitsutaka,Konishi, Takahiro,Kawaguchi, Shinji,Yamada, Masatoshi,Nagata, Toshiaki,Yamano, Mitsuhisa
scheme or table, p. 1178 - 1184 (2011/12/16)
A practical synthetic method for the synthesis of the chiral benzhydrol 8, which is the key intermediate of the squalene synthase inhibitor TAK-475 (1), has been developed. The method, via asymmetric hydrogenation of the benzophenone 7, employed Noyori's ruthenium precatalyst of the type [RuCl 2(diphosphine)(diamine). We focused on tuning of the chiral diphosphine, and have discovered a novel ligand, DADMP-BINAP (18c), for the catalyst that has allowed reduction of the operating pressure in the asymmetric hydrogenation. The precatalyst containing 18c performed effectively at low hydrogen pressure (1 MPa) with sufficient enantioselectivity, and the result enabled us to successfully obtain enantiomerically pure 8 on a multikilogram scale.
Ruthenium-I0D0-optically active phosphine complex
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, (2008/06/13)
This invention is concerned with a ruthenium-iodo-optically active bidentate phosphine complex of the formula (I):[Ru-(I)q-(T1)n(SOL)r(L)]m(T2)p(I)s(I)wherein T1 represents a carboxylic acid anion, SOL represents a polar solvent, L represents an optically active bidentate phosphine ligand, T2 represents an anion different from halogen atom anions and carboxylic acid anions, n denotes 0 or 1, r denotes 0, 3 or 4, m denotes 1 or 2, q denotes 0 or 1, or where m is 2, q may represent 1 or 1.5, p denotes 0 or 1, and s denotes 0, 1 or 2 is prepared. Said phosphine complex is usefull as an efficient catalyst for asymmetrically hydrogenating 4-methylene-2-oxetanone into optically active 4-methyl-2-oxetanone.
