4-(3'-fluorophenyl)-cyclohexanone

Synthesis

The compound (CAS:217476-14-7) (61.9 g) was added to a reaction vessel with formic acid (120 g) and toluene (120 ml) under nitrogen protection. After heating and refluxing the reaction for 3 hours, it was slowly cooled to room temperature. To the reaction mixture, water (300 ml) and toluene (300 ml) were added, mixed thoroughly and left to stand until it was layered into organic and aqueous phases. The organic phase was separated and washed sequentially with saturated aqueous sodium bicarbonate and water, followed by drying with anhydrous magnesium sulfate. The solvent was removed by distillation under reduced pressure and the residue was purified by column chromatography using a solvent mixture of toluene and ethyl acetate (toluene: ethyl acetate = 9:1, v/v) as eluent and silica gel as stationary phase. The target fraction was collected and dried to give 47.2 g of 4-(3-fluorophenyl)cyclohexanone (19) in 93.7% yield (calculated based on compound (18)).

References

[1] Patent: EP2206695, 2010, A1. Location in patent: Page/Page column 57-58
[2] Patent: EP2279990, 2011, A1. Location in patent: Page/Page column 51
[3] Journal of the American Chemical Society, 2012, vol. 134, # 41, p. 17023 - 17026,4
[4] Journal of the American Chemical Society, 2012, vol. 134, # 41, p. 17023 - 17026
[5] Journal of the American Chemical Society, 2012, vol. 134, # 49, p. 20208 - 20208