Hydrochloric Acid → Rosuvastatin impurity 42

tert-Butyl-2-[(4R,6S)-6-hydroxymethyl-2,2-dimethyl-[1,3]dioxan-4-yl]acetate (100.0 g), methanol (700.0 mL), water (100.0 mL), and sodium hydroxide (30.7 g) were added to a reactor. The reaction mixture was stirred at 40˜50° C. for over 8 hours. The reaction was monitored with thin layer chromatography (ethyl acetate/n-hexane=1:1). The reaction mixture was cooled to 15˜20° C. and then the pH of the reaction mixture was adjusted to 4.0˜4.2 using 6N hydrochloric acid solution. The reaction mixture was concentrated under reduced pressure to remove the solvent. Ethyl acetate (800.0 mL) and sodium sulfate (100.0 g) were added to the resulting residue, which was then stirred for over 1 hour. The resulting suspension was filtered under reduced pressure. The filtrate was washed with ethyl acetate (200.0 mL) and then concentrated under reduced pressure to obtain [(4R,6S)-6-hydroxymethyl-2,2-dimethyl-[1,3]dioxan-4-yl]-acetic acid (80.0 g, yield 102%) as a gel form.

1. temperatureThe reaction mixture was cooled to 15˜20° C.
2. concentrationThe reaction mixture was concentrated under reduced pressure
3. customto remove the solvent
4. additionEthyl acetate (800.0 mL) and sodium sulfate (100.0 g) were added to the resulting residue, which
5. stirringwas then stirred for over 1 hour
6. filtrationThe resulting suspension was filtered under reduced pressure
7. washThe filtrate was washed with ethyl acetate (200.0 mL)
8. concentrationconcentrated under reduced pressure

ORD record

ord-bda01d47d3cf4da480be866fb9b0c3a1

Source dataset

uspto-grants-2013_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08476432B2