Hydroxy-substituted azetidinone compounds useful as hypocholesterolemic agents

A process for preparing a compound of the formula ##STR72## wherein:

• Ar.sup.1 and Ar.sup.2 are independently selected from the group consisting of aryl and R.sup.4 -substituted aryl:
• Ar.sup.3 is aryl or R.sup.5 -substituted aryl;
• X, Y and Z are independently selected from the group consisting of --CH.sub.2 --, --CH(lower alkyl)- and --C(dilower alkyl)-;
• R.sup.2 is --OH, --O(lower alkyl) or --O-benzyl:
• R.sup.1 and R.sup.3 are independently selected from the group consisitng of hydrogen, lower alkyl and aryl;
• Pl r is 0 or 1;
• m, n and p are independently 0, 1, 2, 3 or 4;
• provided that the sum of m, n. p and r is 1, 2, 3, 4, 5 or 6, and further provided that when r and n are each zero, p is 1, 2, 3 or 4;
• R.sup.4 is 1-5 substituents independently selected from the group consisting of lower alkyl, --OH. --O(lower alkyl), --O-benzyl, --NR.sup.6 R.sup.7, --COOR.sup.6, --CONR.sup.6 R.sup.7, --COR.sup.6, --SO.sub.2 NR.sup.6 R.sup.7, S(O).sub.0-2 R.sup.9, -(lower alkylene)COOR.sup.6, --CH.dbd.CH--COOR.sup.6, --CF.sub.3, --CN, --NO.sub.2 and halogen;
• R.sup.5 is is 1-5 substituents independently selected from the group consisting of --OH, --O(Iower alkyl), --O-benzyl --NR.sup.6 R.sup.7, --COOR.sup.6, --CONR.sup.6 R.sup.7, --COR.sup.6, --SO.sub.2 NR.sup.6 R.sup.7, S(O).sub.0-2 R.sup.9, -(lower alkylene)-COOR.sup.6 and --CH.dbd.CH--COOR.sup.6 ;
• R.sup.6, R.sup.7 and R.sup.8 are independently selected from the group consisting of hydrogen, lower alkyl, aryl and aryl-substituted lower alkyl;
• and
• R.sup.9 is lower alkyl, aryl or aryl-substituted lower alkyl, comprising:
• (a) treating with a strong base in an anhydrous organic solvent a lactone of the formula ##STR73## wherein X, Y, Z, R.sup.1, R.sup.3, m, n, r and p are as defined above, with the further proviso that if n and r are each zero, p is 1, 2, 3 or 4;
• Ar.sup.10 is Ar.sup.1 as defined above, a suitably protected hydroxy-substituted aryl or a suitably protected amino-substituted aryl;
• and R.sup.2' is R.sup.2 as defined above or a suitably protected hydroxy group;
• (b) reacting the product of step (a) with an imine of the formula ##STR74## wherein Ar.sup.20 is Ar.sup.2, a suitably protected hydroxy-substituted aryl or a suitably protected amino-substituted aryl, and Ar.sup.30 is Ar.sup.3, a suitably protected hydroxy-substituted aryl or a suitably protected amino-substituted aryl;
• c) quenching the reaction with an acid;
• and
• d) removing as necessary a protecting group from any of substituents R.sup.2', Ar.sup.10, Ar.sup.20 and Ar.sup.30 to obtain a compound wherein R, Ar.sup.1, Ar.sup.2 and Ar.sup.3 are as defined above.