Synthesis
GENERAL STEPS: Sodium methanolate (25.00 mg, 0.46 mmol) was dissolved in anhydrous methanol (4.50 mL) and dry dichloromethane (30.00 mL) under nitrogen protection and cooled to 0 °C. Dichloroacetonitrile (5.00 g, 45.50 mmol) was slowly added to this stirred solution and stirring was continued for 1 hour at 0°C. Subsequently, L-serine methyl ester hydrochloride (7.00 g, 45.50 mmol) was added and the reaction mixture was warmed to 25 °C and stirred for 12 hours. Upon completion of the reaction, water was added and the aqueous phase was extracted with dichloromethane (3 x 25.00 mL). The organic layers were combined, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The crude product was dissolved in dichloromethane (50.00 mL) and N,N-diisopropylethylamine (11.90 mL, 68.30 mmol) was added. The reaction mixture was stirred at 50 °C for 5 hours, followed by continued stirring at 25 °C for 12 hours. At the end of the reaction, water was added and the aqueous phase was extracted with dichloromethane (3 x 25.00 mL). The organic layers were combined, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The product did not require further purification (quantitative yield).ESI-MS m/z: 176 [M + H]+, 198 [M + Na]+; 1H NMR (300 MHz, CDCl3) δ 3.92 (s, 3H), 4.63 (s, 2H), 8.25 (s, 1H).
References
[1] Tetrahedron Letters, 2016, vol. 57, # 8, p. 920 - 923
