Methyl iodide → Ethyl 5-bromo-2-methyl-2-phenyl-pentanoate

Participants

Reaction Conditions

Reaction Steps

Under Ar atmosphere, to a solution of ethyl phenylacetate (42.4 g, 0.257 mol) and DMPU (5 mL) in THF (250 mL) was added drop-wise LDA (2.0 M solution in heptane/THF/ethylbenzene, 135 mL, 270 mmol) at −78° C. After 2 h, methyl iodide (41.40 g, 0.292 mol) was added and the mixture was allowed to warn to rt overnight. This solution was cooled to −78° C. and 1,3-dibromopropane (72.7 g, 0.36 mol) was added. The reaction mixture was allowed to stir overnight, gradually warming to rt. After careful addition of ice (200 g), sat. NH4Cl solution (400 mL), and concd. HCl (100 mL), the mixture was extracted with ethyl acetate (2×200 mL). The combined organic layers were dried over MgSO4, concentrated in vacuo, and distilled under reduced pressure to give 5-bromo-2-methyl-2-phenyl-pentanoic acid ethyl ester (88.6 g, 59%) as a colorless oil (bp.: 122-128° C./0.25 mmHg). 1H NMR (300 MHz, CDCl3/TMS): d (ppm): 7.34-7.21 (m, 5H), 4.12 (q, 2H, J=6.9 Hz), 3.35 (t, 2H, J=6.6 Hz), 2.20-1.95 (m, 2H), 1.77-1.71 (m, 2H), 1.56 (s, 3H), 1.18 (t, 3H, J=6.9 Hz). 13C NMR (75 MHz, CDCl3/TMS): d (ppm): 175.88, 143.40, 128.54, 126.90, 125.99, 60.96, 49.83, 38.18, 34.01, 28.45, 22.81, 14.17.

Provenance & Evidence