Pyrrole → 3-Ethyl-2-methoxy-6-methyl-5-pyrrol-1-yl-pyridine

Participants

Reaction Conditions

Reaction Steps

Into each of 2 microwave vials is added 3-bromo-5-ethyl-6-methoxy-2-methyl-pyridine (200 mg, 0.869 mmol), potassium carbonate (180 mg, 1.30 mmol), copper iodide (16 mg, 0.084 mmol), sodium hydroxide (84 mg, 2.10 mmol) and pyrrole (72 μL, 1.04 mmol). The vials are flushed with N2 before anhydrous dimethylformamide (5 mL) is added then sealed. The first reaction is heated in the CEM Discover microwave at 185° C. (max wattage set to 150 W) for 1 hr. LC/MS shows the reaction is incomplete. The reaction is re-microwaved at 185° C. for a further 1 hr but LC/MS shows no further apparent product formation. The second reaction is microwaved at 185° C. for 1 hr. Further copper iodide (150 mg) is added, the reaction is flushed with N2 and re-microwaved at 185° C. for a further 1 hr. LC/MS shows the reaction is largely complete. The two reactions are combined, diluted with water and extracted with three portions of dichloromethane. The combined organic layers are washed with two portions of 1 M aqueous sodium hydroxide, dried over magnesium sulfate and evaporated to give a black oil. The crude product is purified by flash chromatography on a 5-gram silica gel cartridge by elution with ethyl acetate:heptane (1:49, increasing to 1:1). Clean fractions containing the product are combined and evaporated to give 3-ethyl-2-methoxy-6-methyl-5-pyrrol-1-yl-pyridine (68 mg, 18% yield) as a yellow-orange oil. MS: m/e=217 (M+H); 1H NMR (CDCl3, δ ppm): 7.26 (1H, s, obscured by CHCl3 in CDCl3), 6.73 (2H, m), 6.30 (2H, m), 3.98 (3H, s), 2.58 (2H, q), 2.27 (3H, s), 1.10 (3H, t).

Provenance & Evidence