Preparation and application of 1-(3-bromophenyl)pyrrole_Kain Industrial Additive

Background and overview^[1]

1-(3-Bromophenyl)pyrrole is an important pharmaceutical intermediate. For example, it can be used to prepare lithium 3-(pyrrolidin-1-yl)benzenesulfinate from 1,3-dibromobenzene. Prepared by reaction with pyrrolidine.

Preparation^[1]

Synthesis of 1-(3-bromophenyl)pyrrole: Add 1,3-dibromobenzene (20g, 84.78mmol, 1.00 equiv) in toluene (300 mL). To this was added pyrrolidine (6.03g, 84.80mmol, 1.00equiv). Pd(OAc)₂ (190 mg, 0.85 mmol, 0.01 equiv) was then added. BINAP (760 mg, 2.53 mmol, 0.03 equiv) was then added thereto. To this mixture was added Cs₂CO₃ (69.1g, 211.96mmol, 2.50equiv). The resulting reaction solution was allowed to react overnight with stirring while maintaining its temperature at 120°C in an oil bath. The reaction progress was monitored by TLC (EtOAc/PE=1:5). filter. The filtrate was concentrated by evaporation on a rotary evaporator under vacuum. The residue was purified by eluting the column with a PE solvent system. 8.51 g (45%) of 1-(3-bromophenyl)pyrrole were obtained as a pale yellow solid. LC-MS (ES, m/z): [M+H]⁺ Calculated value for C10H13BrN: 226, found value: 226.

Apply^[1]

1-(3-Bromophenyl)pyrrole can be used to prepare lithium 3-(pyrrolidin-1-yl)benzenesulfinate: Purge a 250 mL 3-neck round bottom with an inert atmosphere of nitrogen and maintain it. A solution of 1-(3-bromophenyl)pyrrole (8.51 g, 37.64 mmol, 1.00 equiv) in THF (200 mL) was added to the flask. BuLi (18.07 mL, 45.18 mmol, 1.20 equiv, 2.5 M) was added dropwise to the above material while cooling to -78°C while stirring. The resulting solution was allowed to react with stirring for 1 hour while maintaining its temperature at -78°C in liquid nitrogen. To the mixture was added SO₂ (4.82g, 75.31mmol, 2.00equiv). The resulting solution was allowed to react with stirring for an additional hour while maintaining its temperature at room temperature. The reaction progress was monitored by TLC (EtOAc/PE=1:1). The resulting solution was diluted with 800 mL of n-hexane. The product was precipitated by addition and the filter cake was collected. 8.2 g (100%) of lithium 3-(pyrrolidin-1-yl)benzenesulfinate were obtained as an orange solid.