1,3-Dibromobenzene → Methyl 6-(3-bromophenyl)-1,4,5,6-tetrahydrocyclopenta[b]pyrrole-2-carboxylate

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Reaction Steps

The title compound was synthesized in two steps. First, methyl 6-oxo-1,4,5,6-tetrahydrocyclopenta[b]pyrrole-2-carboxylate (0.503 g, 2.81 mmol) and (3-bromophenyl)magnesium bromide (synthesized in situ) were reacted according to General Procedure 3 to give the carbinol-containing compound methyl 6-(3-bromophenyl)-6-hydroxy-1,4,5,6-tetrahydrocyclopenta[b]pyrrole-2-carboxylate. (Note: (3-Bromophenyl)magnesium bromide was synthesized as follows: Activated magnesium (0.308 g, 12.67 mmol) was placed in a flask and anhydrous THF (50 mL) was added. 1,3-dibromobenzene (1.6 mL, 13.2 mmol) and a catalytic amount of 12 was added. The solution was stirred gently at ambient temperature for 30 min. Additional anhydrous THF (25 mL) was added and the solution refluxed for 3 h, and then allowed to cool to ambient temperature). Methyl 6-(3-bromophenyl)-6-hydroxy-1,4,5,6-tetrahydrocyclopenta[b]pyrrole-2-carboxylate was hydrogenated according to General Procedure 6 (with Pt2O), and was purified by column chromatography (Isco CombiFlash) eluting with a gradient of 0-30% EtOAc/heptane affording the product as a slightly yellow solid: 0.213 g (83% yield). 1H NMR (400 MHz, ACETONE-d6) δ ppm 2.27 (ddt, J=13.19, 8.32, 5.23, 5.23 Hz, 1H), 2.58-2.67 (m, 1H), 2.71-2.79 (m, 1H), 2.90-3.01 (m, 1H), 3.73 (s, 3H), 4.30 (dd, J=8.64, 5.17 Hz, 1H), 6.62-6.65 (m, 1H), 7.10-7.14 (m, 1H), 7.21-7.26 (m, 1H), 7.28-7.30 (m, 1H), 7.35-7.40 (m, 1H), 10.67 (br. s, 1H); LCMS (ESI+) 344.0 (M+Na).

Provenance & Evidence