Methyl 4-chloro-3-(trifluoromethyl)benzoate → Methyl 4-cyclopentyl-3-(trifluoromethyl)benzoate

To zinc(II) chloride (0.5 M solution in tetrahydrofuran, 88.0 mL, 44.0 mmol) was added cyclopentylmagnesium chloride (2 M solution in ether, 20.5 mL, 41.1 mmol). The resulting suspension was stirred at room temperature for 1 h. To the above suspension was added methyl 4-chloro-3-(trifluoromethyl)benzoate (7.00 g, 29.3 mmol) and bis(tri-tert-butylphosphine)palladium (1.35 g, 2.64 mmol) at room temperature. The mixture was heated under reflux for 2 h. The mixture was allowed to cool to room temperature, quenched with saturated aqueous sodium bicarbonate solution and filtered. The filtrate was extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate, concentrated under reduced pressure and purified by silica gel column chromatography to give the title compound as an oil (7.64 g). LCMS m/z=273.2 [M+H]+; 1H NMR (400 MHz, CDCl3) δ ppm 1.57-1.66 (m, 2H), 1.68-1.82 (m, 2H), 1.82-1.94 (m, 2H), 2.04-2.21 (m, 2H), 3.33-3.49 (m, 1H), 3.93 (s, 3H), 7.54 (d, J=8.21 Hz, 1H), 8.13 (dd, J=8.34, 1.77 Hz, 1H), 8.27 (s, 1H).

1. temperatureThe mixture was heated
2. temperatureunder reflux for 2 h
3. temperatureto cool to room temperature
4. customquenched with saturated aqueous sodium bicarbonate solution
5. filtrationfiltered
6. extractionThe filtrate was extracted with ethyl acetate
7. dry with materialThe organic layer was dried over anhydrous sodium sulfate
8. concentrationconcentrated under reduced pressure
9. custompurified by silica gel column chromatography

ORD record

ord-bb1791824e764e9691aba4869aa6214f

Source dataset

uspto-grants-2014_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08853419B2