Diazomethane → HCID 90409108, compound

Participants

Reaction Conditions

Reaction Steps

To a vigorously stirred 0° C. biphasic solution of Et2O (10 mL), 40% aq. KOH (2 mL, 14.0 mmol) and water (2 mL) was added portionwise N-methyl-N′-nitro-N-nitrosoguanidine (0.844 g, 2.87 mmol) over 15 min. When addition had been completed, the ether layer was separated and dried with KOH pellets. The contents were allowed to stand for 5 min, then redried over fresh KOH pellets. To 5 mL of the diazomethane solution (˜50% of total volume) was added a 0° C. solution of (E)-methyl 5-(1-(3-fluoro-5-((tetrahydro-2H-pyran-2-yl)oxy)phenyl)-2-oxabicyclo[2.2.2]octan-4-yl)pent-2-enoate (0.3 g, 0.717 mmol) in THF (2 mL). A mixture of PdOAc2 (0.016 g, 0.072 mmol) in THF (2 mL) was added slowly and the reaction was stirred at 0° C. for 15 min and then the remainder of the diazomethane solution (˜5 mL) was added slowly. The reaction was allowed to warm to rt and stirred for 1 h, then was filtered and then concentrated in vacuo. The residual crude oil was chromatographed (SiO2; gradient from 0% to 30% EtOAc/hexane over 10 min) to give the title compound (0.26 g, 0.601 mmol, 84% yield) as a clear oil. 1H NMR (CDCl3) δ: 6.86 (t, J=1.8 Hz, 1H), 6.74 (ddd, J=10.1, 2.4, 1.5 Hz, 1H), 6.68 (dt, J=10.5, 2.3 Hz, 1H), 5.40 (t, J=3.2 Hz, 1H), 3.93-3.84 (m, 1H), 3.83-3.76 (m, 2H), 3.68 (s, 3H), 3.62 (dtt, J=11.4, 4.1, 1.9 Hz, 1H), 2.03-1.94 (m, 5H), 1.88-1.81 (m, 2H), 1.75-1.56 (m, 7H), 1.43-1.16 (m, 7H), 0.75-0.68 (m, 1H); 19F NMR (CDCl3) δ: −112.1.

Provenance & Evidence