Synthesis
Sodium methanol solution (2.3 g Na, 0.10 mol, 1.0 eq., dissolved in 75 ml of methanol) was slowly added dropwise to a stirred mixture of guaiacol (12.5 g, 0.100 mol, 1.0 eq.) and dimethyl 2-chloromalonate (19.0 g, 0.114 mol, 1.14 eq.). The reaction mixture was stirred at 45 °C for 1 hour. After completion of the reaction, the volatiles were evaporated by rotary evaporator. The residue was dissolved in toluene and washed sequentially with deionized water and 1% aqueous sodium bicarbonate. The organic phase was dried over anhydrous sodium sulfate and concentrated under reduced pressure to give 20.0 g (78.7% yield) of dimethyl 2-(2-methoxyphenoxy)malonate as a viscous oil. The product characterization data were as follows: boiling point 131 °C (literature value 128 °C); 1H NMR (CDCl3) δ 7.12-7.00 (m, 2H), 6.98-6.90 (m, 1H), 6.90-6.82 (m, 1H), 5.27 (s, 1H), 3.85 (s, 3H), 3.84 (s, 6H); 13C NMR ( CDCl3) δ 166.2 (2C), 150.4,146.0,124.4,120.8,119.0,112.5,78.4,55.8,53.0 (2C); HRMS calculated value of C12H14O6 255.0869 (M+H+), measured value 255.0870 (M+H+).
References
[1] European Journal of Medicinal Chemistry, 2016, vol. 121, p. 658 - 670
[2] Organic Preparations and Procedures International, 2016, vol. 48, # 6, p. 481 - 491
[3] Bioorganic and Medicinal Chemistry, 2001, vol. 9, # 4, p. 897 - 907
[4] Patent: US5292740, 1994, A
[5] Patent: WO2011/24056, 2011, A2. Location in patent: Page/Page column 19
