Synthesis
The general procedure for the synthesis of ethyl 2-benzyloxyacetate from ethyl bromoacetate and benzyl alcohol was as follows: 47 ml (0.454 mol) of benzyl alcohol was added dropwise over a period of 30 minutes to a mixture of 21.8 g (0.545 mol) of 60% sodium hydride (NaH) suspended in 1000 ml of anhydrous toluene. The mixture was stirred at room temperature for 4 hours. Subsequently, the suspension was cooled in a water-ice bath and 66 ml (0.595 mol) of ethyl bromoacetate was added dropwise over 45 min. The reaction mixture was heated to room temperature and stirring was continued for 1 hour. The entire mixture was poured into ice water (1200 ml) acidified with 10 ml of concentrated hydrochloric acid. The organic and aqueous phases were separated and the aqueous phase was extracted three times (3x) with ether. The combined organic phase was washed with brine and dried with anhydrous magnesium sulfate. After filtration to remove the desiccant, the organic solvent was removed by evaporation under reduced pressure. The residue was purified by reduced pressure distillation. Ultimately, 66.7 g (76% yield) of ethyl 2-benzyloxyacetate was obtained as a colorless liquid (boiling point Tb = 104-106 °C/ 0.7 torr). The product was characterized by 1H NMR (500 MHz, CDCl3) and mass spectrometry (MS-ESI): 1H NMR δ: 7.39-7.28 (m, 5H), 4.63 (s, 2H), 4.23 (q, J = 7.1 Hz, 2H), 4.09 (s, 2H), 1.28 (t, J = 7.1 Hz, 3H).MS-ESI: ( m/z) calculated value for C11H14O3 [M + H]+: 195.23; measured value: 195.1.
References
[1] Patent: WO2014/16789, 2014, A1. Location in patent: Page/Page column 29
[2] Patent: US5942515, 1999, A
[3] Patent: WO2016/157091, 2016, A1. Location in patent: Page/Page column 20-21
[4] Tetrahedron, 2009, vol. 65, # 34, p. 6925 - 6931
[5] European Journal of Medicinal Chemistry, 2017, vol. 138, p. 630 - 643
