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

Temperature

-78 °C

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.

1. temperatureto warm to 0° C
2. custom2 h and then quenched by addition of 100 mL of 5% aqueous KHSO4
3. extractionextracted with Et2O (200 mL)
4. washThe organic phase is successively washed with 5% aqueous KHSO4, 5% aqueous NaHCO3, H2O, and brine
5. dry with materialdried over Na2SO4
6. concentrationconcentrated in reduced pressure
7. additionA mixture of the residue and 1M aqueous NaOH in MeOH
8. stirringis stirred at 70° C
9. waitAfter 5 h at 70° C.
10. customthe reaction mixture is quenched by 5% aqueous KHSO4 (100 mL)
11. extractionextracted with Et2O (200 mL)
12. washThe organic phase is successively washed with H2O, and brine
13. dry with materialdried over Na2SO4
14. filtrationThe solution is filtered
15. customthe solvent is evaporated in vacuo

ORD record

ord-9ccf03e1903b4815909e44b4769f5429

Source dataset

uspto-grants-2012_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08163773B2