Process for trans-6-[12-(substituted-pyrrol-1-yl)alkyl]pyran-2-one inhibitors of cholesterol synthesis

A process for the preparation of the compound of Formula I.sub.a ##STR48## which comprises (a) reacting 4-methyl-3-oxo-N-phenylpentanamide with benzaldehyde in the presence of a catalyst selected from the group consisting of piperidine and glacial acetic acid, ethylene diamine and glacial acetic acid, and .beta.-alanine and glacial acetic acid and an inert solvent for about 24 to about 36 hours at about 60.degree. C. to about 120.degree. C. to afford the compound of Formula XVIII ##STR49## (b) reacting the compound of Formula XVIII with 4-fluorobenzaldehyde in the presence of a catalyst, selected from the group consisting of 3-benzyl-5-(2-hydroxyethyl)-4-methylthiazolium chloride, 3,4-dimethyl5-(2-hydroxyethyl)thiazolium iodide, 3-ethyl-5-(2-hydroxyethyl)-4-methyl-thiazolium bromide and thiamine hydrochloride, a base, selected from the group consisting of N,N-diisopropylethylamine, pyridine, N,N-dimethylaniline, triethylamine, 1,8-diazabicyclo [5.4.0]undec-7-ene, 1,4-diazabicyclo[2.2.2]octane, 4-dimethylaminopyridine, and N,N,N.sup.1,N.sup.1 -tetramethylethylenediamine, and an inert solvent four about 20 to about 30 hours at about room temperature to about the reflux temperature to afford the compound of Formula XVII ##STR50## (c) reacting the compound of Formula XVII with a compound of Formula ##STR51## wherein R.sub.10 and R.sub.11 are alkyl of one to eight carbon atoms or R.sub.10 and R.sub.11 together are ##STR52## or --CH.sub.2 CH.sub.2 CH.sub.2 -- in the presence of a catalyst selected from the group consisting of R.sub.4 CO.sub.2 H, wherein R.sub.4 is CH.sub.3, CF.sub.3, ClCH.sub.2 --, C.sub.6 H.sub.5 CH.sub.2 CH.sub.2 --, C.sub.6 H.sub.5 CH.sub.2 --, HO.sub.2 CCH.sub.2 --, HO.sub.2 CCH.sub.2 CH.sub.2 --, C.sub.6 H.sub.5 --, para--Cl--C.sub.6 H.sub.5 --, ClCH.sub.2 CH.sub.2 --, meta--H.sub.3 C--C.sub.6 H.sub.5 --, para--H.sub.3 C--C.sub.6 H.sub.or tertiary--C.sub.4 H.sub.9 --, and triethylamine hydrochloride and an inert solvent for about 24 to about 48 hours at about 5.degree. C. to about the reflux temperature of the solvent to afford a compound of Formula XVI. ##STR53## wherein R.sub.10 and R.sub.11 are alkyl of one to eight carbon atoms or R.sub.10 and R.sub.11 together are ##STR54## or --CH.sub.2 --CH.sub.2 --CH.sub.2 --

• (d) and converting a compound of Formula XVI to the compound of Formula XV by acid hydrolysis, ##STR55## (e) reacting the compound of Formula XV with methyl acetoacetate and a base to afford the compound of Formula XIV ##STR56## (f) reacting the compound of Formula XIV with a reducing metal hydride in a solvent to afford the compound of Formula XIII ##STR57## (g) reacting the compound of Formula XIII with a base and neutralizing with an acid to afford the compound of Formula XII ##STR58## (h) the compound of Formula XII is dissolved in a water immiscible solvent to afford the compound of Formula I.sub.a .