Methyl iodide → Benzeneacetic acid, alpha-methyl-, ethyl ester

Participants

Reaction Steps

Under N2 atmosphere, a solution of ethyl phenylacetate (800.0 g, 4.87 mol) in anhydrous THF (6.4 L) was cooled to −40° C. and a solution of LDA (2.0 M in heptane/THF, ethylbenzene, 2.43 L, 4.86 mol) was added dropwise over 30 min. The reaction mixture was stirred for 1 h, and methyl iodide (968 g, 6.82 mol) was added dropwise over 20 min, followed by the addition of DMPU (320 mL). After 1 h, the reaction mixture was allowed to warm to room temperature and stirred overnight. The reaction mixture was poured into water (6.4 L) and extracted with ethyl acetate (3×1.6 L). The combined organic layers were washed with saturated aqueous NH4Cl solution (1.6 L), 1 N HCl (1.6 L), saturated aqueous NaHCO3 solution (1.6 L), and saturated aqueous NaCl solution (1.6 L). The solution was dried over MgSO4 and concentrated in vacuo. The residue was distilled in high vacuo to give 202 (620.0 g, 72%) as a colorless oil. Bp 55-60° C./0.2 Torr (lit. (Shiner, V. J. et al. J. Am. Chem. Soc. 1961, 83, 593-598) by 59-60° C./0.3 Torr). 1H NMR (CDCl3): δ 7.36-7.18 (m, 5H), 4.11 (m, 2H), 3.69 (q, 1H, J=7.1), 1.49 (d, 3H, J=7.1), 1.19 (t, 3H, J=7.1). 13C NMR (CDCl3): δ 174.44, 140.73, 128.57, 127.48, 127.04, 60.66, 45.59, 18.66, 14.16.

Provenance & Evidence