Trimethyl phosphonoacetate → (E)-Methyl 5-(1-(3-(tetrahydro-2H-pyran-2-yloxy)phenyl)-2-oxabicyclo[2.2.2]octan-4-yl)pent-2-enoate

Participants

Reaction Conditions

Reaction Steps

To a 0° C. suspension of LiCl (55.4 mg, 1.306 mmol) in MeCN (2 mL) under N2 was added trimethyl phosphonoacetate (0.188 mL, 1.306 mmol) and DBU (0.197 mL, 1.31 mmol). The reaction was stirred at 0° C. for 30 minutes, and then 3-(1-(3-(tetrahydro-2H-pyran-2-yloxy)phenyl)-2-oxabicyclo[2.2.2]octan-4-yl)propanal (300 mg, 0.871 mmol) was added. The reaction was stirred at rt for 2 h and concentrated in vacuo. The residue was diluted with Et2O, washed with 1 N aq. HCl, satd aq. NaHCO3, brine, dried (MgSO4), filtered, and concentrated in vacuo. The crude oil was purified by flash chromatography on SiO2 (0 to 30% EtOAc:hexanes) to afford the title compound (300 mg, 86% yield) as a white solid. LCMS, [M+NH4]+=418.2. 1H NMR (500 MHz, CDCl3) δ 7.23 (t, J=8.0 Hz, 1H), 7.14-7.11 (m, 1H), 7.03-6.93 (m, 3H), 5.86 (dt, J=15.7, 1.5 Hz, 1H), 5.45 (t, J=3.2 Hz, 1H), 3.94 (ddd, J=11.3, 9.9, 3.0 Hz, 1H), 3.84 (s, 2H), 3.75 (s, 3H), 3.65-3.59 (m, 1H), 2.23-2.15 (m, 2H), 2.09-1.98 (m, 5H), 1.89-1.84 (m, 2H), 1.75-1.58 (m, 8H), 1.37-1.31 (m, 2H).

Provenance & Evidence