Org Prep Daily

January 23, 2010

2-formyl-5-methylpyrrole-4-carboxylic acid

Filed under: procedures — milkshake @ 9:57 am

D-glucosamine hydrochloride 6.470g (Acros; 30mmol) was suspended in methanol 100mL and tert-butyl acetoacetate 9.50g (60mmol) was added, followed by triethylamine 8.5 mL (61 mmol). The mixture was refluxed on a 80C bath for 1 hour with vigorous stirring. The reaction mixture was evaporated and the residue was dissolved in water (about 150mL) with potassium carbonate 2.8g (solid, 20 mmol) added. The mixture was extracted twice with ether (2x150mL) and the organic phases were back-extracted twice with additional water (2x150mL). [The organic phases were discarded]. The combined aqueous extracts containing the pyrrole product were transferred into a 1L beaker, fresh ether 100mL was added and the mixture was placed on ambient water cooling bath. With vigorous stirring, a solution of KI04 29.0g (135 mmol) in water (about 150mL) was gradually added over 15 min period with vigorous stirring (delayed gas evolution and foaming!).  When the potassium periodate addition was complete the mix was stirred for extra 30 min. More ether (400mL) was added and the mixture was shaken and separated. The aqueous phase was re-extracted with additional ether 200mL. The organic phases were washed saturated aq. sodium bicarbonate three times (3x250mL), combined, dried (MgSO4) and evaporated. The syrupy residue gradually solidified on highvac.

This crude tert-butyl ester-aldehyde (5.05g) was dissolved in neat TFA 60mL. After 30 min the dark mixture was evaporated to dryness. The obtained solid residue was suspended in water, the solids were collected by filtration, washed thoroughly with water on the Buchner funnel, dried by suction and then on highvac. Y=2.940g of a tan solid (64% overall)

1H(d6-DMSO; 400MHz): 12.384 (br s, 1H), 12.105(very br s, 1H), 9.405(s, 1H), 7.263(d, 2.5Hz, 1H), 2.454(s, 3H)

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