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. name: Diethyl 2-methylenemalonate
nBuLi solution (2.5 M in hexanes, 2.2 mL, 5.5 mmol) was added, dropwise over 2 min., to a cooled (-20 C bath maintained by an immersion cooler) solution of N,N,N?-trimethylethylenediamine (587 mg, 5.74 mmol) in 2-MeTHF (13 mL). After stirring for 15 min., 1- naphthaldehyde (813 mg, 5.21 mmol) was added dropwise via syringe by mass difference over 1-2 min. After 15 min., more nBuLi solution (2.5 M in hexanes, 6.2 mL, 16 mmol) was added, dropwise over 5 min. After stirring at this temperature for 24 h, the reaction mixture was cooled in a dry ice/acetone bath. Diethyl ketomalonate (3.46 mL, 22 mmol) was then added to the rxn. mixture, dropwise over 5 min. After 5 min., the reaction was quenched by rapid addition of 10. % aq. NH4Cl, and cooling was ended. The resulting mixture was partitioned between dichloromethane and brine. The aqueous layer was extracted once more with dichloromethane, and the combined organic layers were dried (sodium sulfate) and evaporated to afford a yellow oil that darkened over time. Chromatographic purification (144 g silica gel, heptane to 3:7 EtOAc/heptane gradient) afforded the title compound as a mixture with an amine side product.2 The chromatography fractions containing the title compound were washed with 1.0 M aq. HCl and brine, dried (sodium sulfate), and evaporated to afford the title compound as a clear, yellow oil (503 mg, 29 % yield, ca. 85 % purity). LCMS (ESI) m/z: 353.1 [M+Na] (48 %). 1H NMR (400 MHz, CDCl3) delta 1.31 (t, J = 7.1 Hz, 3H), 1.36 (t, J = 7.1 Hz, 3H), 2.50 (s, 1H), 4.26 (dq, J = 10.8, 7.1 Hz, 1H), 4.34 (dq, J = 10.8, 7.1 Hz, 1H), 4.38 (dq, J = 10.7, 7.1 Hz, 1H), 4.42 (dq, J = 10.7, 7.1 Hz, 1H), 6.38 (s, 1H), 7.27 (d, J = 8.9 Hz, 1H), 7.39 (ddd, J = 8.2, 6.9, 1.2 Hz, 1H), 7.55 (ddd, J = 8.3, 6.9, 1.3 Hz, 1H), 7.80-7.88 (m, 2H), 7.94 (d, J = 8.3 Hz, 1H).
These compound has a wide range of applications. It is believed that with the continuous development of the source of the synthetic route 3377-20-6, its application will become more common.
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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