Furo[2,3-c]pyridine-5-carboxylic acid (9CI)

Synthesis

The general procedure for the synthesis of furo[2,3-c]pyridine-5-carboxylic acid from furo[2,3-c]pyridine-5-carboxaldehyde was as follows: furo[2,3-c]pyridine-5-carboxaldehyde (850 mg, 5.8 mmol) was dissolved in 10 mL of dimethyl sulfoxide (DMSO). To this solution was added a 3 mL aqueous solution of potassium dihydrogen phosphate (KH2PO4, 221 mg, 1.6 mmol) followed by a 7 mL aqueous solution of sodium chlorite (NaClO2, 920 mg, 8.2 mmol). The reaction mixture was stirred for 3 h at room temperature. After completion of the reaction, the reaction mixture was diluted with 25 mL of water, the pH was adjusted to 10 with 2 N sodium hydroxide (NaOH) solution, and then extracted with ether (3 x 20 mL). The combined ether layers were discarded. The aqueous layer was adjusted to pH 3.5 with 10% aqueous hydrochloric acid (HCl) solution and then extracted with 10% methanol/dichloromethane (MeOH/CH2Cl2, 13 × 10 mL). The combined organic layers were dried with anhydrous sodium sulfate (Na2SO4), filtered and concentrated in vacuum to give a light-colored oil. Residual DMSO was removed at room temperature under a stream of nitrogen (N2) to give a white paste. The paste was dissolved in methanol (MeOH) and concentrated to dryness. The white solid was washed with ether and dried to give the crude furano[2,3-c]pyridine-5-carboxylic acid (94% yield). The compound with molecular formula C8H5NO3 was obtained by mass spectrometry (ESI) analysis with a mass-to-charge ratio (m/z) of 162.8 (M-H)-.

References

[1] Patent: US2003/153595, 2003, A1
[2] Patent: US2003/45540, 2003, A1
[3] Patent: WO2004/52894, 2004, A1. Location in patent: Page 36
[4] Journal of Medicinal Chemistry, 2006, vol. 49, # 14, p. 4425 - 4436