Hydrochloric Acid → (4-Cyclopentyl-3-(trifluoromethyl)phenyl)methanol

Temperature

85.5 °C

To a solution of 4-cyclopentyl-3-(trifluoromethyl)benzoate (224 g, 823 mmol) in 1,4-dioxane (600 mL), LiBH4 (494 mL, 987 mmol, 2 M solution in THF) was added dropwise at 22° C. The resulting suspension was stirred at 85.5° C. for 5.5 h. The dark brown solution was cooled to 0° C. and the pH adjusted to 5 by slowly adding 6 N HCl (130 mL). The layers were separated and to the aqueous phase H2O (250 mL) and NaCl (20 g) were added. The combined aqueous layers were extracted with EtOAc (2×250 mL). The EtOAc layer was added to the previously separated organic phase and the combined organics were concentrated under reduced pressure. The resulting suspension was filtered through a pad of Celite®/Na2SO4 and the solids were washed with EtOAc (3×400 mL). The combined organics were rotary evaporated and the dark brown oily residue was subjected to chromatography on silica to give the title compound as colorless liquid (110 g). LCMS m/z=243.3 [M−H]+; 1H NMR (400 MHz, CDCl3) δ ppm 1.67-1.55 (m, 2H), 1.82-1.69 (m, 2H), 1.95-1.83 (m, 2H), 2.19-2.04 (m, 2H), 3.39 (quintet, J=8.0 Hz, 1H), 4.72 (s, 2H), 7.55-7.46 (m, 2H), 7.62 (s, 1H).

1. temperatureThe dark brown solution was cooled to 0° C.
2. customThe layers were separated and to the aqueous phase H2O (250 mL) and NaCl (20 g)
3. additionwere added
4. extractionThe combined aqueous layers were extracted with EtOAc (2×250 mL)
5. additionThe EtOAc layer was added to the previously separated organic phase
6. concentrationthe combined organics were concentrated under reduced pressure
7. filtrationThe resulting suspension was filtered through a pad of Celite®/Na2SO4
8. washthe solids were washed with EtOAc (3×400 mL)
9. customThe combined organics were rotary evaporated

ORD record

ord-fb49a503000447f59f42600125db5a79

Source dataset

uspto-grants-2014_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08853419B2