Uses
Ethyl N-Methyl-beta-alaninate is an intermediate in the synthesis of Tolafentrine (T531000), which is a dual-selective phosphodiesterase 3/4 inhibitor used in chronic experimental pulmonary hypertension.
Synthesis
1. cool 33% methylamine ethanol solution (100 mL, 805 mmol) in an ice bath at 0 °C.
2. Ethyl acrylate (11.0 mL, 10.1 g, 101 mmol) was added slowly, keeping the reaction temperature at 0 °C with continuous stirring for 2 hours.
3. Gradually warm the reaction mixture to room temperature and continue stirring for 15 minutes.
4. All volatiles were removed by distillation under reduced pressure.
5. The resulting residue (ethyl 3-(methylamino)propionate crude, 11.2 g) was used directly in the subsequent reaction without further purification.
References
[1] Monatshefte fur Chemie, 2011, vol. 142, # 10, p. 1055 - 1059
[2] Journal of the Chemical Society, Perkin Transactions 2: Physical Organic Chemistry (1972-1999), 1980, p. 1739 - 1745
[3] Journal of Heterocyclic Chemistry, 1997, vol. 34, # 1, p. 87 - 91
[4] Liebigs Annalen der Chemie, 1980, # 9, p. 1438 - 1447
[5] Journal of the American Chemical Society, 1949, vol. 71, p. 2129
