2-tert-Butylthiophene → Ethyl 4-[[4-(5-tert-butyl-thiophen-2-yl)-2,2-dimethyl-(2H)-thiochromen-6-yl]-ethynyl]-benzoate

Participants

Reaction Conditions

Reaction Steps

A solution of 2-tert-butylthiophene (105.0 mg, 0.75 mmol) in 2.0 mL of THF was cooled to -78° C. and n-butyllithium (48.1 mg, 0.75 mmol, 0.47 ml of a 1.6M solution in hexanes) was added and the solution warmed to 0° C. during 1.5 hours. A solution of ZnCl2 (163.2 mg, 1.20 mmol) in 3.0 mL THF was slowly added via cannula. The resulting solution was warmed to room temperature, stirred for 40 minutes, and transferred via cannula to a solution of ethyl 4-[(2,2-dimethyl-4-trifluoromethanesulfonyloxy-(2H)-thiochromen-6-yl)ethynyl]-benzoate (Compound 224, 200.0 mg, 0.40 mmol) and tetrakis(triphenylphosphine) palladium(0) (20.0 mg, 0.02 mmol) in 2.0 mL THF. This solution was heated to 50° C. for 2 hours, cooled to room temperature, and the reaction quenched by the addition of saturated aqueous NH4Cl. The solution was extracted with EtOAc and the combined organic layers were washed with H2O and saturated aqueous NaCl before being dried (MgSO4) and concentrated under reduced pressure. The title compound, 110.0 mg (76%), was isolated by column chromatography (5% EtOAc/hexanes) as a colorless solid. 1H NMR (300 MHz, CDCl3) δ: 8.01 (2H, d, J=8.3 Hz), 7.68 (1H, s), 7.56 (2H, d, J 8.3 Hz), 7.36 (2H, m), 6.82 (2H, m), 6.04 (1H, s), 4.39 (2H, q, J=7.1 Hz), 1.46 (6H, s), 1.43 (9H, s), 1.41 (2H, t, J=7.1 Hz).

Provenance & Evidence