反应详情

A solution (0.2 M) of methyl 5-bromo-6-cyclohexyl-4H-thieno[3,2-b]pyrrole-2-carboxylate (from Step 1) in dry DMF was treated with sodium hydride (2 eq., 60% suspension in mineral oil) at 0° C. The reaction mixture was stirred at RT for 30 min then tert-butyl bromoacetate (3 eq.) was added. The reaction was heated to 50° C. for 1 h. After cooling, the solution was diluted with EtOAc and 1 N hydrochloric acid was added. The organic phase was washed with 1 N hydrochloric acid, saturated NaHCO3 solution and brine, dried over sodium sulfate and evaporated in vacuo to give a residue that was purified by flash chromatography (PE:EtOAc, 9:1) to afford the title compound (80%) as a solid. 1H-NMR (400 MHz, DMSO-d6, 300 K, δ) 7.99 (s, 1H), 4.99 (s, 2H), 3.82 (s, 3H), 2.66-2.52 (m, 1H), 1.82-1.21 (m, 101H), 1.42 (s, 9H). MS (ES+) m/z: 456, 458 [M+H]+.

1. temperatureThe reaction was heated to 50° C. for 1 h
2. temperatureAfter cooling
3. additionwas added
4. washThe organic phase was washed with 1 N hydrochloric acid, saturated NaHCO3 solution and brine
5. dry with materialdried over sodium sulfate
6. customevaporated in vacuo
7. customto give a residue that
8. customwas purified by flash chromatography (PE:EtOAc, 9:1)