Methyl Acrylate → Methyl 4-(1-(3-phenoxyphenyl)-2-oxabicyclo[2.2.2]octan-4-yl)butanoate

Participants

Reaction Conditions

Reaction Steps

A mixture of Zn (622 mg, 9.52 mmol), anhydrous pyridine (5 mL) and methyl acrylate (0.95 mL, 9.52 mmol) was warmed to 50° C., after which NiCl2.6H2O (283 mg, 1.19 mmol) was added. The resulting mixture was heated to 65° C. for 1 h and stirred until the color of the solution became reddish-brown, then was cooled to 0° C., after which a solution of 4-(iodomethyl)-1-(3-phenoxyphenyl)-2-oxabicyclo[2.2.2]octane (500 mg, 1.190 mmol) in pyridine (2 mL) was added. The reaction mixture was allowed to warm to rt overnight, then was diluted with EtOAc (10 mL) and the resulting mixture was filtered off through a pad of CELITE®. The filtrate was washed with 1 N aq. HCl and brine, dried (MgSO4), and concentrated in vacuo. The residual crude oil was purified by flash chromatography (SiO2; gradient from 0 to 50% EtOAc:hexanes) to afford the title compound as a colorless oil (318 mg, 73% yield). LCMS, [M+H]+=381, 1H NMR (400M Hz, CDCl3) δ 7.39-7.24 (m, 3H), 7.19-7.06 (m, 3H), 7.04-6.98 (m, 2H), 6.86 (ddd, J=8.1, 2.4, 0.9 Hz, 1H), 3.82 (s, 2H), 3.70 (s, 3H), 2.31 (t, J=7.3 Hz, 2H), 2.10-1.98 (m, 4H), 1.76-1.57 (m, 6H), 1.22-1.12 (m, 2H).

Provenance & Evidence