Probucol → HCID 86602766, compound

Participants

Reaction Conditions

Reaction Steps

To a solution of probucol (19.0 g, 37 mmol) and 2-[2-ethoxy-5-(2-hydroxy-ethyl)-[1,3]dioxolan-4-yl]-ethanol (Ex-14C, 7.6 g, 37 mmol) in tetrahydrofuran (160 mL) was added triphenylphosphine (10.6 g, 41 mmol) and the resulting mixture was cooled to 0° C. Diethyl azodicarboxylate (7.1 g, 41 mmol) was then added dropwise, stirred at 0° C. for 30 min, and allowed to warm to rt. The solution was ultimately heated to 65° C. and stirred for an additional 18 h for the reaction to complete. The reaction mixture was concentrated under reduced pressure to an orange viscous oil and titurated with hexanes and the resulting slurry was stirred at rt for 30 min. The solution was filtered to remove the triphenylphosphine oxide and the filtrate was concentrated under reduced pressure. The residue was subjected to silica gel chromatography (10% ethyl acetate/hexanes with a gradual increase to 30% ethyl acetate/hexanes) to afford 7.4 g (30%) of 2,6-di-tert-butyl-4-[1-(3,5-di-tert-butyl-4-{2-[2-ethoxy-5-(2-hydroxy-ethyl)-[1,3]dioxolan-4-yl]-ethoxy}-phenylsulfanyl)-1-methyl-ethylsulfanyl]-phenol as a white solid. 1H-NMR (300 MHz, CDCl3) δ7.53 (s, 2H), 7.45 (s, 2H), 5.81 (s. 1H), 5.36 (s, 1H), 4.09–4.19 (m, 2H), 3.84–3.92 (m, 4H), 3.59 (q, 2H, J=6.8 Hz), 2.17–2.19 (m, 2H), 2.02–2.05 (m, 1H), 1.86–1.96 (m, 2H), 1.42–1.44 (m, 42H), 1.19–1.24 (m, 3H). HRMS (ESI) calcd for C40H64O6S2 (M+K), 727.4042; found, 727.4050. Anal. calcd. for C40H64O6S2: C, 66.62, H, 9.55, S, 8.68; found: C, 66.65, H, 9.35, S, 9.01.

Provenance & Evidence