Convenient diastereospecific synthesis of a rociverine precursor and its resolution by lipase-catalyzed transesterification

• Published in: Tetrahedron: asymmetry Vol. 7; no. 12; pp. 3585 - 3592
• Main Authors: Di Bussolo, Valeria, Catelani, Giorgio, Mastrorilli, Ettore, Di Bugno, Cristina, Giorgi, Raffaello
• Format: Journal Article
• Language: English
• Published: OXFORD Elsevier Ltd 01.12.1996; Elsevier
• Subjects: Chemistry; Chemistry, Inorganic & Nuclear; Chemistry, Organic; Chemistry, Physical; Physical Sciences; Science & Technology; ACID
• ISSN: 0957-4166; 1362-511X
• DOI: 10.1016/S0957-4166(96)00467-3

(±)-1-Cyclohexyl- c-2-hydroxymethyl- r-1-cyclohexanol 3, a precursor of the antimuscarinic drug Rociverine 1, was obtained diastereospecifically in very high yield, from the Grignard reaction between C 6H 11MgCl and an appropriately protected 2-(hydroxymethyl)cyclohexanone. The preparation of enantiomerically enriched cis diol (+)-(1R,2S)- 3 and the corresponding 2-acetoxymethyl derivative (+)-(1S,2R)- 12 was achieved by lipase PPL-catalyzed transesterification of racemic diol (±)- 3. (±)-1-Cyclohexyl- c-2-hydroxymethyl- r-1-cyclohexanol 3, a precursor of the antimuscarinic drug Rociverine 1, was diastereospecifically obtained from the Grignard reaction between C 6H 11MgCl and protected 2-(hydroxymethyl)cyclohexanone. The preparation of enantiomerically enriched cis diol (+)-(1R, 2S)- 3 and acetate (+)-(1S,2R)- 12 was achieved by lipase PPL-catalyzed transesterification of racemic diol (±)- 3.