Process for preparing 2-azadihydroxybicyclo{2.2.1}heptane compounds and the l-tartaric acid salt of the compound

摘要

A method according to the invention is directed to the preparation of a 2-azadihydroxybicyclo[2.2.1]heptane compound of formula (I) (I') wherein * represents an R chirality, *' represents an S chirality, R is hydrogen or, respectively, a group of formula (II) (II') wherein R1 is alkyl and Ar is optionally substituted aryl, comprising bishydroxylating a bicyclo[2.2.1]heptene compound of formula (III) (III') wherein *, *' and R are as previously defined, in the presence of about 0.1 mol to about 5 mol % of a metal osmate compound or about 0.06 mol % to about 0.07 mol % osmium tetroxide, and an oxidizing agent capable of regenerating osmium tetroxide. The invention is also directed to the treatment of the (1R) diastereomer of the 2-azadihydroxybicyclo[2.2.1]heptane compound (I) wherein R is a group of formula II with L-tartaric acid, and the L-tartaric acid salt product thereof. Furthermore, the invention is directed to using the (1R) diastereomer of the 2-azadihydroxybicyclo[2.2.1]heptane compound in an acid facilitated acetalizing or ketalizing reaction that results in the protection of the dihydroxy moieties thereof in isopropanol. In addition, the invention is directed to oxidizing a bis O-protected derivative of the (1R) diastereomer of the 2-azadihydroxybicyclo[2.2.1]heptane compound to a corresponding lactam compound in the presence of about 0.01 mol % to about 1 mol % of RuO2 with about 3 equivalents of an oxidant to form the lactam compound with in an enantiomeric excess ("ee") of greater than or equal to about 95%.