Category: 3377-20-6

In the chemical reaction process, reaction time, type of solvent, can easily affect the result of the reaction, thereby determining the yield and properties of the reaction product. An updated downstream synthesis route of 3377-20-6 as follows. Safety of Diethyl 2-methylenemalonate

nBuLi solution (2.5 M in hexanes, 1.4 mL, 3.6 mmol) was added, dropwise over 2 min., to a cooled (dry ice/acetone/ethylene glycol bath at -20 C) solution of N,N,N?-trimethylethylenediamine (388 mg,3.80 mmol) in THF (4.0 mL). After stirring for 15 min., a solution of 4- chlorobenzaldehyde (486 mg, 3.45 mmol) in THF (3.0 mL) was added dropwise over 4 min. Additional THF (2×1.0 mL) was used to complete the transfer. After 15 min., more nBuLi solution (2.5 M in hexanes, 4.3 mL, 11 mmol) was added, dropwise over 4 min. After stirring at this temperature for 2.8 h, the reaction mixture was cooled in a dry ice/acetone bath. After stirring for 10 min., diethyl ketomalonate (2.3 mL, 15 mmol) was added to the reaction mixture, dropwise over 5 min. 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 (3x), and the combined organic layers were dried (sodium sulfate) and evaporated to afford a clear, amber oil (3.30 g) that darkened over time. Repeated chromatographic purification (160 g silica gel, 1:9 to 3:7 EtOAc/heptane gradient followed by 44 g silica gel, 1:9 dichloromethane/heptane to dichloromethane to 1:19 EtOAc/dichloromethane gradient) afforded the title compound as a clear, colorless oil (234 mg, 22 % yield). LCMS (ESI) m/z: 337.2 [M+Na] (42 %). 1H NMR (400 MHz, CDCl3) delta 1.30 (t, J = 7.1 Hz, 3H), 1.33 (t, J = 7.1 Hz, 3H), 2.70 (d, J = 7.6 Hz, 1H), 4.25 (dq, J = 10.8, 7.1, 1H), 4.32 (dq, J = 10.8, 7.1, 1H), 4.33 (dq, J = 10.8, 7.1, 1H), 4.37 (dq, J = 10.8, 7.1, 1H), 5.87 (dt, J = 7.7, 0.6 Hz, 1H), 6.99-7.03 (m, 2H), 7.29-7.35 (m, 1H).

According to the analysis of related databases, 3377-20-6, the application of this compound in the production field has become more and more popular.

Reference:
Article; Rocke, Benjamin N.; Conn, Edward L.; Eisenbeis, Shane A.; Ruggeri, Roger B.; Tetrahedron Letters; vol. 53; 41; (2012); p. 5467 – 5470;,
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

Adding a certain compound to certain chemical reactions, such as: 3377-20-6, name is Diethyl 2-methylenemalonate, belongs to esters-buliding-blocks compound, can increase the reaction rate and produce products with better performance than those obtained under traditional synthetic methods. Here is a downstream synthesis route of the compound 3377-20-6, COA of Formula: C8H12O4

nBuLi solution (2.5 M in hexanes, 2.4 mL, 6.0 mmol) was added, dropwise over 4 min., to a cooled (-20 C bath maintained by an immersion cooler) solution of N,N,N?-trimethylethylenediamine (655 mg, 6.41 mmol) in 2-MeTHF (14 mL). After stirring for 15 min., 4-tert-butoxybenzaldehyde (1.02 g, 5.72 mmol) was added via syringe by mass difference dropwise over 5 min. After 15 min., more nBuLi solution (2.5 M in hexanes, 6.9 mL, 17 mmol) was added, dropwise over 4 min. After stirring at this temperature for 24 h, the reaction mixture was cooled in a dry ice/acetone bath. After stirring for 20 min., diethyl ketomalonate (3.6 mL, 23 mmol) was added to the reaction mixture, dropwise over 8 min. After 5 min., the reaction was quenched by rapid addition of aq. HCl (2.0 M, 12.5 mL), and cooling was ended. The resulting mixture was partitioned between dichloromethane and half-saturated brine. The aqueous layer was extracted once more with dichloromethane, and the combined organic layers were dried (sodium sulfate) and concentrated to a clear, yellow oil (5.45 g). Chromatographic purification (354 g silica gel, heptane to 3:7 EtOAc/heptane gradient) afforded the title compound as a white solid (1.06 g, 53 % yield, ca. 90 % purity). LCMS (ESI) m/z: 375.3[M+Na] (19 %). 1H NMR (400 MHz, CDCl3) delta 1.29 (t, J = 7.1 Hz, 3H), 1.33 (t, J = 7.1 Hz, 3H), 1.35 (s, 9H), 2.48 (d, J = 7.8 Hz, 1H), 4.24 (dq, J = 10.8, 7.1 Hz, 1H), 4.32 (dq, J = 10.8, 7.1 Hz, 1H), 4.34 (dq, J = 10.7, 7.1 Hz, 1H), 4.38 (dq, J = 10.8, 7.1 Hz, 1H), 5.85 (dt, J = 7.8, 0.6 Hz, 1H), 6.64 (dd, J = 8.1, 2.0 Hz, 1H), 6.66 (dt, J = 2.0, 0.5 Hz, 1H), 7.27 (dt, J = 8.2, 0.6 Hz, 1H). 13C NMR (101 MHz, CDCl3) delta 13.9 (1C), 14.1 (1C), 28.8 (3C), 62.7 (1C), 62.7 (1C), 76.1 (1C), 79.3 (1C), 93.6 (1C), 106.4 (1C), 118.2 (1C), 120.2 (1C), 125.3 (1C), 158.6 (1C), 159.3 (1C), 165.3 (1C), 166.4 (1C).

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Reference:
Article; Rocke, Benjamin N.; Conn, Edward L.; Eisenbeis, Shane A.; Ruggeri, Roger B.; Tetrahedron Letters; vol. 53; 41; (2012); p. 5467 – 5470;,
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

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;,
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

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;,
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics