Preparation
synthesis of dimethyl 2-fluoromalonate: Dimethyl malonate (19.8 g, 0.15 mol) and Cu(NO3)2·2.5H2O (3.50 g, 15 mmol) were dissolved in acetonitrile (85 mL), the mixture was cooled to 0–5 °C and stirred at 650 rpm using an overhead stirrer. After purging the system with N2 for 5 minutes, fluorine gas (20% v/v in N2, 50 mL min-1 , 170 mmol) was introduced into the reaction mixture for 7 h. After purging with nitrogen for 20 minutes, the solvent was removed in vacuo and the residue was partitioned between water (30 mL) and ethyl acetate (20 mL). The aqueous phase was extracted with ethyl acetate (2 × 20 mL) and the combined organic layer was washed with saturated brine (20 mL). After drying over sodium sulphate, the solvent was evaporated under reduced pressure to give dimethyl 2-fluoromalonate (21.8 g, 97% yield, 95% purity) as a colourless oil;
IR (neat, cm-1 ) 2962, 1748, 1438, 1250, 1206, 1112, 1016; δH (CDCl3, 400 MHz) 3.85 (6H, s, CH3), 5.31 (1H, d, 2 JHF 48.0, CHF); δF (CDCl3, 376 MHz): -195.73 (d, 2 JHF 48.0, CH–F); δC (CDCl3, 100 MHz) 53.48 (CH3), 85.19 (d, 1 JCF 197.2, C–F), 164.39 (d, 2 JCF 24.0, CvO); m/z (EI+ ) 150 (3%, [M]+ ), 119 (42%, [M-OMe]+ ), 91 (73%, [M-COOMe]+ ), 59 (100%, [COOMe]+ ).
Synthesis
GENERAL PROCEDURE: PhIO (550 mg, 2.5 mmol), Et3N-5HF (800 mg, 4 mmol) and DCE (1 mL) were placed in a PTFE test tube. After stirring for 15 min at room temperature, appropriate amounts of dimethyl malonate (1 mmol) and DCE (1 mL) were added. The test tube was sealed with septum rubber and heated with stirring at 70°C for 24 hours. After completion of the reaction, the reaction mixture was neutralized with aqueous NaHCO3 and the product was extracted with CH2Cl2 (3 x 10 mL). The organic layers were combined, washed with brine (20 mL), dried over anhydrous Na2SO4 and concentrated under reduced pressure. Finally, the product was purified by silica gel column chromatography with hexane-CH2Cl2 mixed solvent as eluent.
References
[1] Green Chemistry, 2015, vol. 17, # 5, p. 3000 - 3009
[2] Journal of Fluorine Chemistry, 1992, vol. 58, # 1, p. 71 - 79
[3] Synthesis (Germany), 2015, vol. 47, # 20, p. 3241 - 3245
[4] Journal of Fluorine Chemistry, 2014, vol. 167, p. 74 - 78
[5] Journal of the Chemical Society, Chemical Communications, 1991, # 3, p. 179 - 181
