Sodium Iodide → Ethyl 3-(4-methoxyphenyl)-2,2-dimethylpropanoate

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Reaction Steps

Ethyl iso-butyrate (35.0 g, 0.30 mol) was added to a solution of lithium N,N-diisopropyl amide (prepared from N,N-diisopropylamine (38.1 g, 0.38 mol) and n-BuLi (207 mL, 0.33 mol, 1.6 M solution in hexanes)) in dry tetrahydrofuran (1 L) at −78° C. over a 30 min period under N2 atmosphere. After the addition was complete, the reaction was stirred for 1 h after which HMPA (100 mL), NaI (67.0 g, 0.44 mol) and 4-methoxybenzyl chloride (39.3 g, 0.25 mol) were added sequentially. The reaction was then warmed to room temperature and stirred for additional 16 h before quenching at 0° C. with saturated NH4Cl solution (250 mL) and the mixture was extracted with EtOAc (2×1 L). The combined organic layers were washed successively with 2 N HCl (2×300 mL), saturated sodium bicarbonate solution (2×300 mL), and brine (400 mL), dried over Na2SO4 and filtered. Concentration of the filterate and purification of the resulting residue by flash column chromatography (silica gel, 100:0 to 96:4 hexane/EtOAc) afforded 54.0 g (90%) of ethyl 2,2-dimethyl-3-(4-methoxyphenyl)propanoate as a light yellow oil; 1H NMR (200 MHz, CDCl3) δ 7.03 (d, J=8.7 Hz, 2H), 6.79 (d, J=8.7 Hz, 2H), 4.10 (q, J=7.3 Hz, 2H), 3.78 (s, 3H), 2.78 (s, 2H), 1.23 (t, J=7.3 Hz, 3H), 1.15 (s, 6H).

Provenance & Evidence