Uses
3,4-bis(2-Methoxyethoxy)benzoic Acid Ethyl Ester is a compound used in the synthesis of Erlotinib (E625008), a cancer treatment medicine.
Synthesis
(3) Preparation of ethyl 3,4-bis(2-methoxyethoxy)benzoate 13: Ethyl 3,4-dihydroxybenzoate 12 (5 g, 27.45 mmol) was placed in a 250 mL two-necked flask and acetone (100 mL), potassium carbonate (9.48 g, 68.63 mmol), potassium iodide (0.5 g) and 2-bromoethyl methyl ether ( 7.84 mL, 82.35 mmol). The reaction mixture was heated to reflux at 60 °C for 19 hours. Upon completion of the reaction, the reaction solution was cooled to 5 °C and stirred for 30 min, followed by filtration and concentration to dryness. The resulting solid was dried by oil pumping for 22 h to give the khaki colored solid product 13 (8.19 g, 100% yield).1H-NMR (CDCl3) data: δ 1.32 (t, 3H, J = 7Hz), 3.41 (s, 6H), 3.76 (m, 4H), 4.15 (m, 4H), 4.29 (q, 2H, J = 7Hz), 6.85 (d, 1H, J = 8.4Hz), 7.53 (dd, 1H, J = 8.4Hz, J = 2.3Hz), 7.63 (dd, 1H, J = 8.4Hz, J = 2.3Hz).
References
[1] Patent: US2010/267949, 2010, A1. Location in patent: Page/Page column 6
[2] Patent: EP1614676, 2006, A1. Location in patent: Page/Page column 194
[3] Patent: EP2163546, 2016, B1. Location in patent: Paragraph 0125
[4] European Journal of Medicinal Chemistry, 2008, vol. 43, # 7, p. 1478 - 1488
[5] Chemistry - A European Journal, 2015, vol. 21, # 41, p. 14342 - 14346
