Probucol → 2,6-di-tert-butyl-4-(1-{3,5-di-tert-butyl-4-[2-(2,2-dimethyl-[1,3]dioxolan-4(S)-yl)-ethoxy]-phenylsulfanyl}-1-methyl-ethylsulfanyl)-phenol

Participants

Reaction Conditions

Reaction Steps

A 1 L round bottom flask equipped with a nitrogen adapter, temperature probe and addition funnel was charged with 9.3 g (58 mmol, 1.3 eq) of (s)-(+)-2,2-dimethyl-5-oxo-1,3-dioxolane-4-ethanol (Ex-10A), 500 mL of anhydrous THF, 25.6 g (98.3 mmol, 2.2 eq) of triphenylphosphine and 23.1 g (44.7 mmol, 1 eq) of probucol. The reaction mixture was cooled to 0° C. with an ice bath, 14.0 mL (89.4 mmol, 2.0 eq) of diethyl azodicarboxylate was charged to the addition funnel and then added dropwise to the reaction mixture. The dark reaction mixture was warmed to ambient temperature and stirred for 18 hours. The reaction mixture concentrated under reduced pressure and the residue was purified by silica gel chromatography (2% EtOAc/hexanes gradient to 5% EtOAc/hexanes) to yield 8.2 g of 2,6-di-tert-butyl-4-(1-{3,5-di-tert-butyl-4-[2-(2,2-dimethyl-[1,3]dioxolan-4(S)-yl)-ethoxy]-phenylsulfanyl}-1-methyl-ethylsulfanyl)-phenol as a white solid, mp 44–46° C. 1H NMR (300 MHz, CDCl3) δ: 7.56 (s, 2H), 7.47 (s, 2H), 5.38 (s, 1H), 4.61 (dd, J=9.17 and 3.75 Hz, 1H), 3.92–4.00 (m, 1H), 3.79–3.87 (m, 1H), 2.50–2.61 (m, 1H), 2.15–2.27 (m, 1H), 1.47 (s, 6H), 1.46 (s, 18H), 1.45 (s, 18H). HRMS (EI+) m/z+Na: calc. 681.3623; found 681.3619.

Provenance & Evidence