Ammonium Chloride → 1-(4-Ethoxy-2,3-difluorophenyl)-4-(3-propylcyclopentyl)cyclohexanol

Temperature

-78 °C

THF (100 ml) was added to 1-bromo-4-ethoxy-2,3-difluorobenzene(5.1 g) in a reaction vessel under an atmosphere of nitrogen, and the mixture was cooled to −78° C. n-Butyllithium (1.57 M, in a hexane solution) (13.8 ml) was added dropwise at a temperature of −70° C. or lower. The stirring was continued at −78° C. for another 2 hours, and 4-(3-propylcyclopentyl)-cyclohexanone (3.0 g) in a THF (10 ml) solution was added dropwise at a temperature of −70° C. or lower. After the mixture had been stirred at −78° C. for another 1 hour, it was warmed to room temperature, and a saturated aqueous solution of ammonium chloride (50 ml) was added. The mixture was separated, and the water layer was extracted with ethyl acetate three times, and then the combined organic layer was washed with brine. The solution was dried over anhydrous magnesium sulfate and the solvent was distilled off under reduced pressure. The residue was purified by silica gel chromatography (eluent: ethyl acetate/n-heptane= 1/9 by volume) to give 1-(4-ethoxy-2,3-difluorophenyl)-4-(3-propylcyclopentyl)cyclohexanol (5.0 g).

1. temperatureit was warmed to room temperature
2. customThe mixture was separated
3. extractionthe water layer was extracted with ethyl acetate three times
4. washthe combined organic layer was washed with brine
5. dry with materialThe solution was dried over anhydrous magnesium sulfate
6. distillationthe solvent was distilled off under reduced pressure
7. customThe residue was purified by silica gel chromatography (eluent: ethyl acetate/n-heptane= 1/9 by volume)

ORD record

ord-68b31ef77df246b59bf6f6bed1b04037

Source dataset

uspto-grants-2014_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08685274B2