Grad Dip Arylpyrrole

Ethyl 1-(4-fluorophenyl)-2,5-dimethyl-1<em>H</em>-pyrrole-3-carboxylate was synthesised with a yield of 7.7g, progressed to hydrolysis.

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Reaction Start time: 11:00 AM EST 15/1/13

Potassium carbonate (11.2 g, 81 mmol, 1.3 equiv.) and sodium iodide (10.1 g, 68 mmol, 1.1 equiv. ) were stirred in acetonitrile (50 mL) and cooled in an ice bath. Ethyl acetoacetone (8.0 mL, 62 mmol, 1 equiv.) followed by chloroacetone (6.4 mL, 80 mmol, 1.3 equiv.) were added dropwise. The mixture was heated to 90 °C and left overnight. At 10:00 AM the next day, the mixture was filtered then concentrated under reduced pressure. The concentrated mixture was then washed with water (2 × 20 mL) and with brine (2 × 20 mL). The product was dried then concentrated under reduced atmosphere giving a brown oil (6.4 g) which was used in the second step without further purification.

4-fluoroaniline was added at 4:00 PM and the reaction was heated to 90 °C and left overnight. The reaction was cooled and dissolved with ethyl acetate (25 mL) then washed with water (2 × 20 mL), followed by brine (1 × 20 mL). The mixture was then concentrated under reduced pressure to give a brown liquid, which was recrystallised with EtOH (40 mL) and 40% EtOH (20 mL). Brown crystals formed (7.7 g, 29 mmol, 47% yield).

See also: Synthesis of Ethyl 1-(4-fluorophenyl)-2,5-dimethyl-1H-pyrrole-3-carboxylate (MD 1-1) Upscaled Synthesis of Ethyl 1-(4-fluorophenyl)-2,5-dimethyl-1H-pyrrole-3-carboxylate (JRC 1-1) Synthesis of ethyl 2-acetyl-4-oxopentanoate intermediate. (LMW 7-1) Synthesis of Ethyl 1-(4-fluorophenyl)-2,5-dimethyl-1H-pyrrole-3-carboxylate (PMY 6-1)

Risk and Hazard Assessment:
Same as Synthesis of Ethyl 1-(4-fluorophenyl)-2,5-dimethyl-1H-pyrrole-3-carboxylate (MD 1-1)