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

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, 5 H), 4.11 (m, 2 H), 3.69 (q, 1 H, J=7.1), 1.49 (d, 3 H, J=7.1), 1.19 (t, 3 H, 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.

1. waitAfter 1 h
2. stirringstirred overnight
3. extractionextracted with ethyl acetate (3×1.6 L)
4. washThe 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)
5. dry with materialThe solution was dried over MgSO4
6. concentrationconcentrated in vacuo
7. distillationThe residue was distilled in high vacuo

ORD-Eintrag

ord-dc6776b1a1a846e3a6f212d5b53a2644

Quelldatensatz

uspto-grants-2014_02

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08642653B2