SUMMARY
Pyrrole-ring labeled (\left[{ }^{14} \mathrm{C}\right]) atorvastatin (Lipitor 8 , CI-981), [ (\left.\mathrm{R}-\left(\mathrm{R}^{}, \mathrm{R}^{}\right)\right]-2-) (4-fluorophenyl)- (\beta, \gamma)-dihydroxy-5-(1-methylethyl)-3-phenyl-4-[(phenylamino)carbonyl]-1H-[3- (\left.{ }^{14} \mathrm{C}\right]) pyrrole-1-heptanoic acid calcium salt (2:1) ((\mathbf{1 5})), was synthesized in a 5 -step synthesis from (\left[7-{ }^{14} \mathrm{C}\right]) benzaldehyde ((\mathbf{5})) with an overall yield of 6.9 to (9.6 %). Thus, Knoevenagel condensation of 5 with isobutyrylacetanilide (6) gave 4-methyl-3-oxo-N-phenyl-2-(phenyl (\left[{ }^{14} \mathrm{C}\right]) methylene)pentamide (7). Stetter condensation of (7) with (p)-fluorobenzaldehyde ( (\underline{\mathbf{8}}) ), in the presence of the catalyst 3-ethyl-5-(2-hydroxyethyl)-4-methylthiazolium bromide ( (\underline{9}) ) and triethylamine, gave the key labeled intermediate diketone, 4fluoro- (\alpha)-(2-methyl-1-oxopropyl)- (\gamma)-oxo-N, (\beta)-diphenylbenzene (\left[3-{ }^{14} \mathrm{C}\right]) butaneamide (10). Reaction of 10 with the protected chiral dihydroxyaminoheptanoic ester, [4R-cis]-1,1-dimethylethyl-6-(2-aminoethyl)-2,2-dimethyl-1,3-dioxane4-acetate (11), synthesized separately, gave atorvastatin in its protected form, [4R-cis]-1,1-dimethylethyl-6-[2[2-(4-fluorophenyl)-5-(1-methylethyl)-3phenyl-4-[íphenylamino)carbonyl]-1H-[3- (\left.{ }^{14} \mathrm{C}\right]) pyrrol-1-yl]ethyl]-2,2-dimethyl1,3-dioxane-4-acetate (12). Deprotection of 12 led to the sodium salt 13 . Subsequent calcium salt formation gave the ring-labeled atorvastatin 15 .