Morpholine → methyl 4-(3,4-dichlorophenyl)-2-(morpholin-4-yl)-6-oxo-5,6-dihydro-4H-cyclopenta[b]thiophene-5-carboxylate

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Reaction Conditions

Reaction Steps

A mixture of methyl 2-bromo-4-(3,4-dichlorophenyl)-6-oxo-5,6-dihydro-4H-cyclopenta[b]thiophene-5-carboxylate (0.25 g, 0.59 mmol), morpholine (0.26 g, 2.94 mmol), tris(dibenzylideneacetone)dipalladium(0) (26.9 mg, 0.03 mmol), 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (34.0 mg, 0.06 mmol) and cesium carbonate (0.58 g, 1.76 mmol) in 1,4-dioxane (5.96 mL) was heated at 80° C. under argon for 3 h. And the temperature was raised to 100° C. and maintained overnight. The mixture was dryloaded on silica gel and purified by column chromatography (12 g cartridge, gradient hexanes to 60% EtOAc in hexanes) and then preparative HPLC to afford the product as a white solid (0.8 mg, 0.3%). LCMS: (FA) ES+ 426, 428, 430. 1H NMR (400 MHz, CDCl3) δ 7.37 (d, J=8.0 Hz, 1H), 7.24 (d, J=2.1 Hz, 1H), 6.99 (dd, J=8.0, 2.1 Hz, 1H), 5.77 (s, 1H), 4.73 (d, J=3.2 Hz, 1H), 3.86-3.76 (m, 7H), 3.67 (d, J=3.2 Hz, 1H), 3.35-3.26 (m, 4H).

Provenance & Evidence