Hydrochloric Acid → Atorvastatin

Participants

Reaction Steps

The crude (3R,5R)-7-[2-(4-fluorophenyl)-5-isopropyl-3-phenyl-4-phenylcarbamoyl-pyrrol-1-yl]-3,5-dihydroxy-heptanoic acid, t-butyl ester (VI-A) was converted to the acid using an excess of KOH/MeOH/Water, followed by lactonization in toluene with catalytic HCl. Chiral HPLC analysis (ChiralCel OF; 1 ml/min; 60° C.; 254 nm; 20% IPA:Hexanes) tR(3R,5R)=26.97 min./tR(3S,5S)=33.8 min. tR(3R,5S)=38.1 min./tR(3S,5R)=61.0 min.) indicated an enantiomeric excess of the syn isomer of 85%, favoring the (R,R) configuration.

Provenance & Evidence