Ethyl isobutyrate → HCID 90415236, compound

Temperature

0 °C

To a mixture of diisopropylamine (8.00 mL, 57.1 mmol) in THF (300 mL) cooled to 0° C. was added n-BuLi (24.60 mL, 61.5 mmol) dropwise. The mixture was stirred at 0° C. for 1 h. Then to the mixture cooled to −30° C. was added a solution of ethyl isobutyrate (6.12 g, 52.7 mmol) in THF (2 mL). The mixture was stirred at −30° C. for 1 h. To the mixture was added a solution of 1-(bromomethyl)-2-(trifluoromethyl)benzene (10.5 g, 43.9 mmol) in THF (5 mL) at −30° C. The whole mixture was stirred at −30° C. for 3 h and then stirred at 25° C. for 12 h. The mixture was quenched with NH4Cl (aq) and extracted with EA. The organic layer was washed with brine, dried over MgSO4, filtered and concentrated. The crude material was purified on silica column chromatography (PE/EA=200:1). All fractions found to contain product by TLC (PE/EA=10:1, Rf=0.6) were combined and concentrated to yield a light yellow solid of ethyl 2,2-dimethyl-3-(2-(trifluoromethyl)phenyl)propanoate (10 g, 35.3 mmol, 80.0% yield): 1H NMR (400 MHz, CDCl3) δ: 7.62 (d, J=8.0 Hz, 1H), 7.41 (t, J=7.6 Hz, 1H), 7.29 (t, J=7.6 Hz, 1H), 7.22 (d, J=8.0 Hz, 1H), 4.17 (q, J=7.2 Hz, 2H), 3.14 (s, 3H), 1.25 (t, J=7.2 Hz, 3H), 1.18 (s, 6H); ES-LCMS m/z 275 (M+H).

1. temperatureThen to the mixture cooled to −30° C.
2. stirringThe mixture was stirred at −30° C. for 1 h
3. stirringThe whole mixture was stirred at −30° C. for 3 h
4. stirringstirred at 25° C. for 12 h
5. customThe mixture was quenched with NH4Cl (aq)
6. extractionextracted with EA
7. washThe organic layer was washed with brine
8. dry with materialdried over MgSO4
9. filtrationfiltered
10. concentrationconcentrated
11. customThe crude material was purified on silica column chromatography (PE/EA=200:1)
12. concentrationconcentrated

ORD record

ord-d5531f815e774e118556ccac31a5bc8e

Source dataset

uspto-grants-2015_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08937071B2