HCID 73441861, compound → HCID 86713718, compound

Participants

Reaction Steps

Palladium hydroxide on carbon (˜50% water, 10 wt % palladium, 7.1 g, 5 mmol) was added to a slurry of C40 (22.0 g, 50.3 mmol) and ammonium formate (80.2 g, 1.27 mol) in methanol (500 mL), and the reaction mixture was stirred for 2.5 hours at room temperature, then combined with similar reactions run on C41 (24.5 g, 56.0 mmol) and filtered through Celite, rinsing with methanol (1 L). The filtrate was concentrated in vacuo and treated with aqueous sodium hydroxide solution (0.2 M, roughly 800 mL), while keeping the pH at approximately 9. This was extracted three times with ethyl acetate (0.5 L, 1 L and 0.5 L), and the combined organic layers were washed with saturated aqueous sodium chloride solution, dried over magnesium sulfate, and concentrated under reduced pressure to afford the product as a light yellow oil. Hydrogenation was assumed to have occurred on the less hindered face; the assigned stereochemistry was also supported by the IC50 obtained on the final product 8, which indicated that the tetrahydrofuran moiety bore the substituents in a cis orientation (see Table 1). Yield: 26.3 g, 101 mmol, 95%. 1H NMR (400 MHz, CDCl3) δ 7.53 (br AB quartet, JAB=8 Hz, ΔνAB=50 Hz, 4H), 4.96 (dd, J=7.4, 7.0 Hz, 1H), 3.70-3.77 (m, 1H), 2.93-3.01 (m, 1H), 2.33-2.43 (m, 1H), 2.00-2.10 (m, 1H), 1.66-1.85 (m, 2H), 1.12 (d, J=6.4 Hz, 3H).

Provenance & Evidence