Process for trans-6-(2-(substituted-pyrrol-1-yl)alkyl)pyran-2-one inhibitors of cholesterol synthesis

A process for the preparation of the compound of Formula I-1 ##STR28## and the dihydroxy acid and pharmaceutically acceptable salts thereof, corresponding to the opened lactone ring of the compound of Formula I-1 which comprises:

• (a) reacting the compound of Formula IVa ##STR29## with a compound of Formula V ##STR30## wherein R.sup.8 or R.sup.9 is independently alkyl of from one to ten carbon atoms,
• cyclopropyl,
• cyclobutyl,
• cyclopentyl,
• cyclohexyl,
• benzyl or
• phenyl or
• R.sup.8 and R.sup.9 together are
• --(CH.sub.2).sub.4 --,
• --(CH.sub.2).sub.5 --,
• --(CH(R.sup.10)--CH.sub.2).sub.3 --,
• --(CH(R.sup.10)--CH.sub.2).sub.4 --,
• --(CH(R.sup.10)--(CH.sub.2).sub.2 --CH(R.sup.10))--,
• --(CH(R.sup.10)--(CH.sub.2).sub.3 --CH(R.sup.10))--,
• --CH.sub.2 --CH.sub.2 --O--CH.sub.2 --CH.sub.2 --,
• --CH(R.sup.10)--CH.sub.2 --O--CH.sub.2 --CH.sub.2 --,
• --CH(R.sup.10)--CH.sub.2 --O--CH.sub.2 --CH(R.sup.10)--,
• wherein R.sup.10 is alkyl of from one to four carbon atoms provided R.sup.8 and R.sup.9 are not both methyl;
• and
• R.sup.11 or R.sup.12 is independently
• alkyl of from one to three carbon atoms or phenyl or
• R.sup.11 and R.sup.12 are taken together as
• --(CH.sub.2).sub.n -- wherein n is 4 or 5 in a solvent to afford a compound of Formula IIIa ##STR31## wherein R.sup.8, R.sup.9, R.sup.11, and R.sup.12 are defined as above;
• (b) reacting a compound of Formula IIIa with an acid in a solvent to afford a compound of Formula IIa ##STR32## wherein R.sup.8 and R.sup.9 are as defined above;
• (c)
• (1) hydrolyzing a compound of Formula IIa with a base,
• (2) followed by neutralization with an acid, and
• (3) dissolution and/or heating in a solvent with concomitant removal of water to afford a compound of Formula I-1;
• (d) and if desired converting the resulting compound of Formula I-1 to a dihydroxy acid corresponding to the opened lactone ring of structural Formula I-1 by conventional hydrolysis and further, if desired converting the dihydroxy acid to a corresponding pharmaceutically acceptable salt by conventional means, and if so desired converting the corresponding pharmaceutically acceptable salt to a dihydroxy acid by conventional means, and if so desired converting the dihydroxy acid to a compound of Formula I-1 by dissolution and/or heating in an inert solvent.