Synthesis
The general procedure for the synthesis of 4-bromopyrrole-2-carboxylic acid from 1-(4-bromo-1H-pyrrol-2-yl)-2,2,2-trichloroacetophenone is as follows: a THF solution (5 mL) of 1-(4-bromo-1H-pyrrol-2-yl)-2,2,2-trichloroacetophenone (4.7 mmol) was prepared as described by Belanger et al. ( Tetrahedron Lett. 1979, 2505-2508). The solution was stirred at room temperature and 1 mL of a 10% aqueous NaOH (aq) solution was added and stirring was continued for 1 hour. Upon completion of the reaction, the solvent was removed under reduced pressure and the crude product was partitioned between water and ethyl acetate. Subsequently, the pH was adjusted to 5 with 10% aqueous HCl. The phases were separated and the aqueous layer was extracted again with ethyl acetate. The organic phases were combined and dried with magnesium sulfate. Evaporation of the solvent gave 4-bromo-1H-pyrrole-2-carboxylic acid as a solid, which could be used in the next reaction without further purification. Yield: 64%; LCMS (retention time): 2.74 min (Method B); MS (ES+) gave m/z: 191 and 193.
References
[1] Patent: WO2006/123257, 2006, A2. Location in patent: Page/Page column 63
[2] Patent: WO2007/107319, 2007, A1. Location in patent: Page/Page column 7-8
