BackgroundIf literature protocols are followed, conversion of an advanced ketal ester intermediate (available in kilogram quantities via a published Paal-Knorr synthesis) to cholesterol-lowering drug atorvastatin calcium is hampered by several process issues, particularly at the final stage where the hemi-calcium salt is obtained.ResultsWe developed a high-yielding synthesis of atorvastatin calcium salt on 7 kg scale that affords >99.5% product purities by introducing the following key improvements: i. isolating the pure product of the ketal deprotection step as crystalline solid, and ii. using a convenient ethyl acetate extraction procedure to isolate the pure atorvastatin calcium at the ester hydrolysis and counter-ion exchange step.ConclusionThe convenient and operationally simple conversion of an advanced intermediate of atorvastatin to the clinically used hemi-calcium salt form of the drug that is superior to the methods obtainable from the literature is now available to facilitate the production of atorvastatin calcium on industrial scale.Graphical abstractStepwise ketal and tert-butyl ester group hydrolysis and a modified work-up protocol lead to a more convenient preparation of API-grade atorvastatin calcium.Electronic supplementary materialThe online version of this article (doi:10.1186/s13065-015-0082-7) contains supplementary material, which is available to authorized users.

Treatment of cis-[PtCl 2 (Me 2 SO) 2 ] with the pyrazole acetoximes p-RC 6 H 4 {CN(H)NCCH}CH 2 C(Me)=NOH (R=OMe, H, F, Cl, CN, NO 2 ), prepared by a cascade reaction from the vinyl isoxazoles p-RC 6 H 4 C(H)=C(H){CONCC(NO 2 )}Me, leads to the complexes [PtCl 2 (Ar{CN(H)NCCH}CH 2 C(Me)=NOH)] (71-88 %). The complexes exhibit solid state room temperature phosphorescence with emission maxima in the region of 644-691 nm and biexponential relaxation with t 1 % 2 ms and t 2 % 0.32 ms. In the platinum compounds, substituents R affect phosphorescence quantum yields, which increase by one order of magnitude on going from electron acceptor (R = NO 2 ; 0.2 %) to electron-donor groups (R = OMe; 2.0 %). Based upon theoretical TD-DFT calculations using the CAMÀB3LYP functional, the absorption spectra were attributed to metal-to-ligand charge transfer ( 1 MLCT) and ligand-to-ligand charge transfer ( 1 LLCT) processes. The pyrazole acetoximes and their complexes were characterized by elemental analyses (C, H, N), HRESI-MS, FTIR, 1 H NMR (for metalfree species), and CP-MAS TOSS 13 C{ 1 H} NMR (for the platinum complexes). In addition, two complexes were studied by singlecrystal X-ray diffraction.[a] Dr.

No abstract