TCMDC_ArylPyrrole

 

This procedure details the hydrolysis of the ester (Ethyl 1-(4-fluorophenyl)-2,5-dimethyl-1H-pyrrole-3-carboxylate) into the carboxylic acid ((1-(4-Fluorophenyl)-2,5-dimethyl-1H-pyrrole-3-carboxylic acid), as shown below diagrammatically.



The crude product JRC 1-1 (13.6g, 58.3 mmol, 1 equiv.), was dissolved in EtOH (20mL) and added to an excess of 20% sodium hydroxide (170 mL, 875 mmol, 15 equiv.). The mixture was stirred at rt for 10 min before being heated to 60 °C at 3PM and left overnight. TLC at 11am the following morning showed some starting material remaining, so the mixture was heated to reflux for another 2 hours before being cooled, filtered and washed with water (2 x 20 mL). The solid obtained was dissolved in water (50 mL). Sodium hydroxide (1.5g, 38 mmol, 0.65 equiv) and sodium bicarbonate (2.2 g, 26 mmol, 0.44 equiv.) were added for the purpose of making the solution basic again. Water (100 mL) was added to the basic solution, and the mixture was heated to ensure all product was dissolved before the mixture was washed with ethyl acetate (3 x 30 mL). The inorganic layer was re-acidified (checked with universal indicator papers, pH 2) and vacuum dried to give 9.565 g (41 mmol) of product in 70.32% yield.

TLC: 25% ethyl acetate/hexane. Visualised with UV/vanillin (11am; 14/2/2012)


Risk assessment:


See also:
Upscaled Synthesis of Ethyl 1-(4-fluorophenyl)-2,5-dimethyl-1H-pyrrole-3-carboxylate (JRC 1-1) - previous experiment
Synthesis of TCMDC-123812 via acid chloride (JRC 3-1) - next experiment