Methanol → HCID 178455592, compound

Participants

Reaction Steps

A three necked round bottom flask fitted with a temperature probe, nitrogen inlet, mechanical stirrer and slow addition funnel was charged with N-[(1E)-2-{[tert-butyl(dimethyl)silyl]oxy}ethylidene]-2-methylpropane-2-sulfinamide (176 g, 0.530 mol) and DCM (2 L). At an internal temperature of −65° C., 2-thienyl lithium (1.0 M in THF) (0.794 L, 0.794 mol) was added dropwise such that the internal temperature was maintained <−65° C. The reaction mixture was stirred for 60 minutes, quenched at −65° C. with methanol (0.214 L, 5.30 mol), diluted with NH4Cl (2 L) and warmed to room temperature. The layers were then separated and the aqueous layer was back extracted with DCM (2 L). The combined organic layers were dried over Na2SO4, filtered and concentrated. The crude concentrate was pre-loaded onto silica, divided into 4 batches, and purified by automated flash chromatography (4×1.5 kg SiO2 columns, hexanes:EtOAc; 5% to 50% gradient over to provide the title compound as an amber oil. 1H NMR ((CD3)2CO) δ 7.42 (1H, d, J=4.0 Hz), 7.14 (1H, s), 7.01 (1H, J=4.0, 3.5 Hz), 4.78-4.75 (1H, m), 4.48 (1H, s), 3.95-3.92 (1H, m), 3.86-3.82 (1H, m), 1.23 (9H, s), 0.94 (9H, s), 0.12 (6H, s).

Provenance & Evidence