2-Hydroxy-3-cyanopyridine synthesis

Yield:20577-27-9 100%

Reaction Conditions:

with acetic acid for 12 h;Reflux;

Steps:

2-Bromo-3-cyanopyridine(24).

2-Chloro-3-cyanopyridine 23 (3.68 mg, 26 mmol) was boiled underreflux with AcOH (100 mL) for 12 h. The evaporation residue, in THF (80 mL)and H₂O (20 mL), was boiled under reflux for 4 h. Evaporation gave 3-cyanopyridin-2-one(3.12 g, quant.) as white crystals: mp 110-114°C (lit.¹³174-175°C); ¹H NMR d 6.47 (1 H, t, J =6.6 Hz, 5-H), 7.91 (1 H, dd, J = 6.5, 2.1 Hz, 4-H), 8.14 (1 H, dd, J =7.0, 2.1 Hz, 6-H), 11.48 (1 H, s, 1-H); ¹³C NMR d 105.80 (3-C), 124.05(5-C), 141.87 (CN), 144.50 (6-H), 150.02 (4-C), 154.20 (2-C); MS m/z 143.0214(M + Na)⁺ (C₆H₄N₂NaO requires143.0222). Bu₄NBr (8.55 g, 26 mmol) and P₂O₅(3.67 g, 26 mmol) were heated in PhMe (250 mL) at 80°C for 30 min. The above3-cyanopyridin-2-one (1.59 g, 13 mmol) was added and the mixture was boiledunder reflux for 12 h. The mixture was cooled, poured into cold water andextracted (EtOAc, 2 ×). Drying and evaporation gave 24 (2.24 g, 94%) asoff-white crystals.

References:

Kumpan, Katerina;Nathubhai, Amit;Zhang, Chenlu;Wood, Pauline J.;Lloyd, Matthew D.;Thompson, Andrew S.;Haikarainen, Teemu;Lehti?, Lari;Threadgill, Michael D. [Bioorganic and Medicinal Chemistry,2015,vol. 23,# 13,art. no. 12299,p. 3013 - 3032] Location in patent:supporting information