tert-Butyl (4R-cis)-6-[(acetyloxy)methyl]-2,2-dimethyl-1,3-dioxane-4-acetate

Chemical Properties

White or grey white solid powder

Uses

Tert-butyl 2-[(4R,6S)-2,2-Dimethyl-6-[(methylcarbonyloxy)methyl]-1,3-dioxan-4-yl]acetate (Rosuvastatin Impurity 19) is an impurity of Rosuvastatin (R700500), a selective and competitive HMG-CoA reductase inhibitor.

Synthesis

Tert-butyl (4R,6S)-6-hydroxymethyl-2,2-dimethyl-1,3-dioxane-4-acetate (1.0 g, 3.84 mmol) was dissolved in 10 mL of dichloromethane, and pyridine (0.9 g, 11.52 mmol) was added at room temperature and stirred for 30 min. Acetyl chloride (0.66 g, 8.45 mmol) was then added and stirring was continued at room temperature for 1 hour. After completion of the reaction, 10 mL of water was added to the mixture and the organic layer was separated by stirring for 10 minutes. The aqueous layer was extracted twice with 5 mL of dichloromethane, the organic layers were combined and washed with 10 mL of water to separate the organic layer. The organic layer was dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure to afford 0.98 g (86% yield) of the target product (4R,6S)-tert-butyl (4R,6S)-6-[(acetyloxy)methyl]-2,2-dimethyl-1,3-dioxane-4-acetate as light pink crystals.

References

[1] Patent: KR2016/126700, 2016, A. Location in patent: Paragraph 0161; 0162-0165
[2] Journal of Organic Chemistry, 2011, vol. 76, # 22, p. 9444 - 9451