Triethylamine → 3-(1-Benzenesulfonyl-1H-indol-5-yl)-but-2-enoic acid methyl ester

Participants

Reaction Conditions

Reaction Steps

5-Iodo-N-benzenesulfonylindole (18.09 g, 47 mmol), methyl crotonate (40 mL, 378 mmol), triethylamine (145 mL), and palladium acetate (2.65 g, 11.8 mmol) were combined in DMF (600 mL). The reaction was heated at 100° C. for 4 h. TLC (3:1) hexane:ethyl acetate showed iodide still present. Methyl crotonate (25 mL) and dichlorobis(triphenylphosphine) palladium(II) (3.31 g, 4.7 mmol) was added. The reaction was heated for an additional 4 h and then at room temperature for 13 h at which time starting material was virtually gone. The solids were allowed to settle and most of the liquid decanted off. The remaining portion was filtered through a pad of celite to remove the solids and the volume reduced somewhat in vacuo. The solution was diluted with water (1 L) and washed with diethyl ether (3×500 mL). The organic portion was washed with 1N HCl (2×500 mL), brine (2×500 mL), dried (MgSO4), filtered and evaporated in vacuo to provide 18.3 g of a dark brown oil. The material was purified preparatively in two runs on a Waters 2000LC using a gradient elution of (98:2) ethyl acetate:hexane to 66:34 ethyl acetate:hexane to give 6.79 g (40%). Mp: 80-85° C.

Provenance & Evidence