Synthetic Route of 3377-20-6,Some common heterocyclic compound, 3377-20-6, name is Diethyl 2-methylenemalonate, molecular formula is C8H12O4, traditional synthetic route has been very mature, but the traditional synthetic route has various shortcomings, such as complicated route, low yield, poor purity, etc, below Introduce a new synthetic route.
nBuLi solution (2.5 M in hexanes, 2.5 mL, 6.2 mmol) was added, dropwise over 3 min., to a cooled (dry ice/EtOH/ethylene glycol bath at .20 C) solution of N,N,N?-trimethylethylenediamine (0.90 mL,6.9 mmol) in 2-MeTHF (15 mL). After stirring for 20 min., 2- chlorobenzaldehyde (0.70 mL, 6.2 mmol) was added dropwise, maintaining the internal reaction temperature below .20 C. After 10 min., more nBuLi solution (2.5 M in hexanes, 7.6 mL, 19 mmol) was added dropwise, again maintaining the internal reaction temperature below .20 C. After stirring at this temperature for 2.5 h, the reaction mixture was cooled in a dry ice/acetone bath. Diethyl ketomalonate (4.1 mL, 27 mmol) was added to the reaction mixture dropwise, maintaining the internal reaction temperature below .50 C. After 5 min., the reaction was quenched by rapid addition of aq. HCl (1.0 M, excess), and cooling was ended. The resulting mixture was extracted with dichloromethane (2x), and the combined organic layers were dried (sodium sulfate) and evaporated to afford a clear, orange oil. Repeated chromatographic purification (48 g silica gel, 1:19 to 1:1 EtOAc/heptane gradient; then 48 g silica gel, 1:9 to 2:3 EtOAc/heptane gradient; and finally 54 g silica gel, 1:9 dichloromethane/heptane to dichloromethane to 1:19 EtOAc/dichloromethane gradient) afforded the title compound as a clear, colorless oil (224 mg, 11 % yield). GCMS (EI) m/z: 314 [M+] (6.2 %). 1H NMR (400 MHz, CDCl3) ? 1.28 (t, J = 7.1 Hz, 3H), 1.31 (t, J = 7.1 Hz, 3H), 2.92 (s, 1H), 4.23 (dq, J = 10.8, 7.1 Hz, 1H), 4.30 (dq, J = 10.8, 7.1 Hz, 1H), 4.32 (dq, J = 10.7, 7.1 Hz, 1H), 4.36 (dq, J = 10.7, 7.1 Hz, 1H), 6.00 (s, 1H), 6.90 (d, J = 8.2 Hz, 1H), 6.96 (d, J = 7.9 Hz, 1H), 7.22 (t, J = 8.1 Hz, 1H).
The synthetic route of 3377-20-6 has been constantly updated, and we look forward to future research findings.
Reference:
Article; Rocke, Benjamin N.; Conn, Edward L.; Eisenbeis, Shane A.; Ruggeri, Roger B.; Tetrahedron Letters; vol. 53; 41; (2012); p. 5467 – 5470;,
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