Ethyl isovalerate → 3-Methyl-2-{[2-(trimethylsilyl)ethoxy]methyl}butanoic acid

Participants

Reaction Conditions

Reaction Steps

To a solution of 3-methylbutyric acid ethyl ester (1.3 g, 10 mmol) in THF (50 mL) is added dropwise LDA solution (2 M in THF/hexane/ethylbenzene, 6 mmol) at −78° C., and the mixture is stirred at −78° C. After 0.5 h, to the reaction mixture is added (2-chloromethoxyethyl)trimethylsilane (2.65 mL, 15 mmol) at −78° C. The reaction mixture is allowed to warm to 0° C. 2 h and then quenched by addition of 100 mL of 5% aqueous KHSO4 and extracted with Et2O (200 mL). The organic phase is successively washed with 5% aqueous KHSO4, 5% aqueous NaHCO3, H2O, and brine, then dried over Na2SO4 and concentrated in reduced pressure. A mixture of the residue and 1M aqueous NaOH in MeOH is stirred at 70° C. After 5 h at 70° C., the reaction mixture is quenched by 5% aqueous KHSO4 (100 mL) and extracted with Et2O (200 mL). The organic phase is successively washed with H2O, and brine, then dried over Na2SO4. The solution is filtered and the solvent is evaporated in vacuo to afford the title compound.

Provenance & Evidence