Trimethyl phosphonoacetate → HCID 90408793, compound

Participants

Reaction Steps

A 0° C. mixture of trimethyl phosphonoacetate (0.209 mL, 1.45 mmol), DBU (0.218 mL, 1.45 mmol) and LiCl (0.061 g, 1.45 mmol) in MeCN (5 mL) was stirred for 30 min under N2, after which 3-(1-(3-fluoro-5-((tetrahydro-2H-pyran-2-yl)oxy)phenyl)-2-oxabicyclo[2.2.2]octan-4-yl)propanal (0.35 g, 0.966 mmol) in MeCN (5 mL) was added. The reaction was stirred for 2 h at rt, then was concentrated in vacuo. The residue was diluted with Et2O, and then washed successively with 1N aq. HCl, sat. aq. NaHCO3, and brine, dried (MgSO4), and concentrated in vacuo. The residual crude oil was chromatographed (SiO2; gradient from 0% to 50% EtOAc/hexane over 20 min) to give the title compound (0.30 g, 0.717 mmol, 74.2% yield) as a white solid. 1H NMR (CDCl3) δ: 6.97 (dt, J=15.6, 6.8 Hz, 1H), 6.87 (t, J=1.8 Hz, 1H), 6.75 (ddd, J=10.1, 2.3, 1.4 Hz, 1H), 6.68 (dt, J=10.5, 2.3 Hz, 1H), 5.85 (dt, J=15.6, 1.6 Hz, 1H), 5.40 (t, J=3.2 Hz, 1H), 3.89 (ddd, J=11.3, 10.0, 3.1 Hz, 1H), 3.84-3.81 (m, 2H), 3.75 (s, 3H), 3.62 (dtd, J=11.4, 4.1, 1.4 Hz, 1H), 2.22-2.14 (m, 2H), 2.05-1.98 (m, 4H), 1.88-1.82 (m, 2H), 1.75-1.59 (m, 8H), 1.36-1.30 (m, 2H); 19F NMR (CDCl3) δ: −112.1.

Provenance & Evidence