Hydrochloric Acid → Rosuvastatin

Participants

Reaction Conditions

Reaction Steps

Rosuvastatin tert-butyl ester (27.0 g, 50.2 mmol) is dissolved in 225 mL of a 4:1 mixture of THF/water. The clear solution is warmed to 30° C. and 8.0 M NaOH (6.75 mL, 54.0 mmol) is added portionwise. The reaction mixture is stirred at 30° C. for 2 hours giving a clear yellow solution. Then THF is removed completely under the reduced pressure (20 mbar) at 40° C. The remaining aqueous solution is diluted with water to 225 mL and washed with AcOEt (3×90 mL). To a vigorously stirring solution of sodium rosuvastatinate is added dropwise HCl 37% (4.2 mL, 50.2 mmol) at ambient temperature. The obtained white emulsion of a free acid is extracted with AcOEt (150 mL). After separation from the organic layer aqueous phase is additionaly extracted with AcOEt (2×50 mL). Organic layers are combined and washed with water (3×30 mL). Then AcOEt is removed under reduced pressure (20 mbar) at 40° C. The residue is dissolved in a minimal amount of acetonitrile (MeCN) and the solvent is rapidly evaporated under reduced pressure (20 mbar) at 40° C. to give 25.48 g of the solid residue of free rosuvastatin acid.

Provenance & Evidence