Synthesis
GENERAL METHOD: Benzyl (3-fluorophenyl)carbamate (2 mmol) was dissolved in anhydrous THF (10 mL) and cooled to -78 °C under nitrogen protection. Subsequently, a THF solution of 1 M LHMDS (1.7 mL, 1.7 mmol) was slowly added over 20 min. After stirring the reaction mixture at -78 °C for 1 h, (R)-(-)-glycidyl butyrate (0.24 g, 1.7 mmol) was added dropwise and stirring was continued at this temperature. Next, the reaction mixture was allowed to gradually warm up to room temperature over a period of 1 hour with stirring and stirring was continued for 12 hours. Upon completion of the reaction, the reaction was quenched with deionized water (10 mL) and EtOAc (4 mL) was added. The organic and aqueous layers were separated and the aqueous layer was extracted with EtOAc (3 x 10 mL). The organic extracts were combined, washed with saturated aqueous sodium chloride solution (3 × 5 mL), dried over anhydrous Na2SO4, filtered and concentrated in vacuum. The crude product was dissolved in DCM (10 mL) and left overnight to precipitate a white precipitate, filtered and washed with DCM.
References
[1] Bioorganic and Medicinal Chemistry Letters, 2017, vol. 27, # 23, p. 5310 - 5321
[2] European Journal of Medicinal Chemistry, 2011, vol. 46, # 4, p. 1027 - 1039
[3] Patent: CN106146559, 2016, A. Location in patent: Paragraph 0044; 0045
[4] Bioorganic and Medicinal Chemistry Letters, 1996, vol. 6, # 9, p. 1009 - 1014
[5] Patent: US2010/234615, 2010, A1. Location in patent: Page/Page column 36
