Dimethylformamide → (E)-tert-butyl 2-(3-(4-formylphenyl)acrylamido)-4-(thiophen-2-yl)phenylcarbamate

Participants

Reaction Conditions

Reaction Steps

A suspension of (E)-3-(4-formylphenyl)acrylic acid 93 (1.046 g, 5.94 mmol) in 1,2-dichloroethane (30 mL) was treated with neat thionyl chloride (SOCl2) (0.9 mL, 12.3 mmol) and stirred at 67° C. then dimethyl formamide (0.3 mL) was slowly added; and the reaction mixture was allowed to stir at 67° C. for 30 min, cooled to room temperature, concentrated, diluted with dry benzene (40 mL) and concentrated again. The yellow residue was stored under vacuum for 3 h then suspended in pyridine (25 mL) and treated with amine 4 (1.113 g, 3.83 mmol) and 4-dimethylamino pyridine (DMAP) (156 mg). The suspension was stirred at room temperature for 3 days, diluted with H2O (10 mL) then stirred for additional 5 h. The solution was diluted with DCM, washed with 5% KHSO4, saturated NaHCO3, dried over MgSO4, filtered and concentrated to provide title compound 94 (0.415 g, 24% yield) after purification by flash chromatography (eluent: 30% to 50% AcOEt in hexanes). LRMS: 448.2 (calc) 471.0 (M+Na, obs)

Provenance & Evidence