Tetrahydrofuran → (E)-ethyl 3-(1-(3,4-difluorophenyl)cyclohexyl)acrylate

Participants

Reaction Steps

To a solution of triethyl phosphonoacetate (1.802 mL, 9.00 mmol) in THF (20 mL) at 0° C. was added 1M potassium t-butoxide (9.00 mL, 9.00 mmol) dropwise, and the mixture was stirred at the same temperature. After 15 mins, a solution of 1-(3,4-difluorophenyl)cyclohexanecarbaldehyde (Int. 3-B, 1.009 g, 4 5 mmol) in 10 mL of THF was added, and the mixture was stirred at room temperature for 2 hrs. The mixture was diluted with EtOAc, washed with water and brine, dried over Na2SO4, and evaporated to give an oily residue. The residue was purified by Combiflash (80 g silica gel) eluting with 5:95 EtOAc-hexane to give (E)-ethyl 3-(1-(3,4-difluorophenyl)cyclohexyl)acrylate (Int. 3-C, 608 mg, 45.9% yield for 2 steps) as an oil. 1H NMR (400 MHz, CDCl3) δ ppm 6.98-7.16 (3 H, m), 6.91 (1 H, d, J=15.82 Hz), 5.60 (1 H, d, J=16.26 Hz), 4.17 (2 H, q, J=7.18 Hz), 1.83-2.06 (4 H, m), 1.40-1.61 (6 H, m), 1.27 (3 H, t, J=7.03 Hz).

Provenance & Evidence