Synthesis
General procedure for the synthesis of (R)-2,2-dimethyl-1,3-dioxolane-4-carboxylic acid from methyl (R)-(+)-2,2-dimethyl-1,3-dioxolane-4-carboxylate:
1. To a solution of (R)-2,2-dimethyl-1,3-dioxolane-4-carboxylic acid methyl ester (1.8 g, 11.24 mmol) in tetrahydrofuran (THF, 20 mL), an aqueous solution (20 mL) of lithium hydroxide monohydrate (0.71 g, 16.9 mmol) was slowly added dropwise at 0 °C, and the dropwise addition time was controlled to be within 10 min.
2. After the dropwise addition was completed, the reaction mixture was continued to be stirred at 0 °C for 1 hour.
3. After completion of the reaction, the reaction mixture was diluted with 50 mL of water and extracted with ethyl acetate (50 mL) and the organic layer was discarded.
4. The aqueous layer was acidified to pH=2 with 10 M phosphoric acid (H3PO4).
5. The acidified aqueous layer was extracted with ethyl acetate (50 mL x 4) and the organic layers were combined.
6. The combined organic layers were washed sequentially with water and saturated saline.
7. The organic layer was dried with anhydrous sodium sulfate, filtered and concentrated under reduced pressure to remove the solvent to afford 1.6 g (97% yield) of (R)-2,2-dimethyl-1,3-dioxolane-4-carboxylic acid, which was used directly in the next reaction without further purification.
References
[1] Patent: WO2005/82892, 2005, A2. Location in patent: Page/Page column 72-73
[2] Journal of Agricultural and Food Chemistry, 2010, vol. 58, # 10, p. 6458 - 6464
[3] Bioorganic and Medicinal Chemistry Letters, 2004, vol. 14, # 12, p. 3231 - 3234
[4] Journal of the American Chemical Society, 1998, vol. 120, # 38, p. 9735 - 9747
[5] Tetrahedron Letters, 2004, vol. 45, # 39, p. 7371 - 7373
