1,2-Difluorobenzene → 4-Pentyl(2,3-difluorophenyl)cyclohexanol

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Reaction Steps

1,2-Difluorobenzene (29) (60.5 g) and THF (500 ml) were put in a reaction vessel under a nitrogen atmosphere, and cooled to −73° C. s-Butyllithium (1.06 M, in a n-hexane and cyclohexane solution; 500.0 ml) was added dropwise thereto in the temperature range of −74° C. to −65° C., and the mixture was stirred for another 2 hours. Subsequently, 4-pentylcyclohexanone (40) (89.2 g) in a THF (200 ml) solution was added dropwise thereto in the temperature range of −76° C. to −65° C., and the stirring was continued for another 20 hours while the mixture was allowed to return to 25° C. Then, the reaction mixture was poured into a vessel containing ammonium chloride (55.1 g) and ice-water (1,000 ml), and mixed. Toluene (1500 ml) was added thereto and the mixture was allowed to separate into organic and aqueous phases, and then an extractive operation was carried out. The organic phase was fractionated, and washed sequentially with water and a saturated aqueous solution of sodium hydrogencarbonate and brine, and then dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure, giving 173.5 g of 1-(2,3-difluoropheyl)-4-pentylcyclohexanol (41). The compound (41) was pale-yellow oil.

Provenance & Evidence