Isobutyric Acid → 2,2-Dimethyl-4-phenylbutanoic acid

Temperatur

0 °C

To a stirring mixture of diisopropylamine (2.2 mL, 15 mmol) and sodium hydride [60% in mineral oil] (0.66 g, 16.5 mmol) in dry THF (50 mL), isobutyric acid (1.4 mL, 15 mmol) was dropwise added. The mixture was refluxed for 15 min, cooled to 0° C., and 2.5M n-butyllithium (BuLi) in hexane (5.45 mL, 14 mmol;) was added. After 20 min at 0° C., the mixture was heated to 30-35° C. for 30 min. The solution was then cooled to 0° C. and (2-bromoethyl)-benzene (2.8 mL, 15 mmol) was slowly added over 20 min. After ca. 1 h at 30-35° C. the reaction was quenched by adding water (40 mL), while keeping the temperature below 15° C. The aqueous layer was separated, and the organic layer washed with a mixture of Et2O/H2O (1:1). The aqueous layers were combined, extracted with Et2O (20 mL), acidified with 2M HCl solution, and the product was further extracted with Et2O (2×30 mL). The combined organic layers were washed with brine, dried over Na2SO4, filtered and concentrated under vacuum to afford the title compound (0.619 g, 21%) as a colorless oil. 1H NMR (CDCl3): δ 1.31 (s, 6H), 1.86-1.95 (m, 2H), 2.59-2.68 (m, 2H), 7.17-7.33 (m, 5H).

1. additionwas dropwise added
2. temperatureThe mixture was refluxed for 15 min
3. temperaturethe mixture was heated to 30-35° C. for 30 min
4. temperatureThe solution was then cooled to 0° C.
5. customAfter ca. 1 h at 30-35° C. the reaction was quenched
6. additionby adding water (40 mL)
7. customthe temperature below 15° C
8. customThe aqueous layer was separated
9. washthe organic layer washed with a mixture of Et2O/H2O (1:1)
10. extractionextracted with Et2O (20 mL)
11. extractionthe product was further extracted with Et2O (2×30 mL)
12. washThe combined organic layers were washed with brine
13. dry with materialdried over Na2SO4
14. filtrationfiltered
15. concentrationconcentrated under vacuum

ORD-Eintrag

ord-28b7526c5caf46a09dd6d45dda3f30ad

Quelldatensatz

uspto-grants-2016_05

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US09353075B2