Sodium Bicarbonate → Methyl 4-cyclopentyl-3-(trifluoromethyl)benzoate

Temperature

70 °C

To a solution of 4-chloro-3-(trifluoromethyl)benzoate (196.7 g, 824 mmol) in THF (100 mL), cyclopentylzinc(II) bromide (1979 mL, 989 mmol) was added dropwise at 7.8° C. The temperature at the end of the addition rose to 22° C. Bis(tri-t-butylphosphine)palladium (21.07 g, 41.2 mmol) was added to the dark brown solution at the same temperature, and the resulting mixture was stirred at 70° C. for 8 h. The mixture was added to saturated aqueous NaHCO3 (100 mL) at 0° C., stirred at the same temperature for 30 min and then at 22° C. for 2 h. The resulting suspension was filtered through Celite® and the filtrate concentrated under vacuum. The solids were washed with EtOAc (3×300 mL), the filtrate was combined with the previous concentrate and the combined organics were washed with H2O (2×600 mL), brine (2×500 mL), dried (Na2SO4), decanted and concentrated under reduced pressure to give the title compound as an orange oil (227 g) without further purification. LCMS m/z=273.4 [M+H]+; 1H NMR (400 MHz, CDCl3) δ ppm 1.71-1.60 (m, 2H), 1.83-1.75 (m, 2H), 1.95-1.87 (m, 2H), 2.21-2.11 (m, 2H), 3.46 (quintet, J=8.8 Hz, 1H), 3.97 (s, 3H), 7.58 (d, J=8.4 Hz, 1H), 8.18 (dd, J=8.0 Hz, 1.6 Hz, 1H), 8.31 (d, J=1.6 Hz, 1H).

1. additionThe temperature at the end of the addition
2. customrose to 22° C
3. stirringstirred at the same temperature for 30 min
4. waitat 22° C. for 2 h
5. filtrationThe resulting suspension was filtered through Celite®
6. concentrationthe filtrate concentrated under vacuum
7. washThe solids were washed with EtOAc (3×300 mL)
8. concentrationprevious concentrate
9. washthe combined organics were washed with H2O (2×600 mL), brine (2×500 mL)
10. dry with materialdried (Na2SO4)
11. customdecanted
12. concentrationconcentrated under reduced pressure

ORD record

ord-91a2392ed291474fb086a69ea0cae861

Source dataset

uspto-grants-2016_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09447041B2