Sodium Carbonate → Ethyl 4-(1,4-dioxaspiro[4.5]dec-7-en-8-yl)benzoate

Participants

Reaction Steps

To a cooled (−78° C.) solution of 1,4-cyclohexanedione mono-ethylene ketal (1.00 g, 6.40 mmol) in anhydrous THF (30 mL) was added lithium bis(trimethylsilyl)amide (7.7 mL, 1.0 M in THF, 7.70 mmol) dropwise. After 10 min, a solution of 2-[N,N-bis(trifluoromethylsulfonyl)amino]5-chloropyridine (2.51 g, 6.40 mmol) in THF (10 mL) was added, and the resulting mixture was allowed to warm slowly to ambient temperature overnight, at which point it was quenched by pouring into sat. aq. NaHCO3. The mixture was extracted with EtOAc. The organic phase was separated, dried over anhydrous sodium sulfate, and concentrated in vacuo. To a flask containing the unpurified enol triflate (1.36 g, 4.72 mmol) were added 4-ethoxycarbonylphenylboronic acid (1.10 g, 5.66 mmol) and trans-dichlorobis(triphenylphosphine) palladium (II) (331 mg, 0.472 mmol). Acetonitrile (24 mL) and sodium carbonate (11.8 mL, 1.0 M aqueous, 11.8 mmol) were added and the resulting mixture was degassed via nitrogen sparge. The reaction mixture was stirred at 70° C. for 3 h, then was allowed to cool to ambient temperature and was poured into water. The mixture was extracted with EtOAc, and the organic phase was concentrated in vacuo. Purification by chromatography on silica gel (0 to 30% EtOAc in hexanes, then 30 to 100% EtOAc in hexanes) provided the title compound: LCMS m/z 289.1 [M+H]+; 1H NMR (500 MHz, CDCl3) δ 7.97 (d, J=8.5 Hz, 2H), 7.44 (d, J=8.5 Hz, 2H), 6.12-6.10 (m, 1H), 4.36 (q, J=7.0 Hz, 2H), 4.03 (s, 4H), 2.70-2.67 (m, 2H), 2.50-2.48 (m, 2H), 1.93 (t, J=6.5 Hz, 2H), 1.39 (t, J=7.0 Hz, 3H).

Provenance & Evidence