2,3-dimethyl-5-nitropyridin-4-ol synthesis

Yield:-

Reaction Conditions:

with sulfuric acid;nitric acid at 60 - 75; for 3.25 h;

Steps:

264.3

Anhydrous potassium acetate (49 g, 0.5 mol) was added to a solution of2,3-dimethyl-4-nitropyridine (45.6 g, 0.3 mol) prepared in Step 2 in 300 ml of acetic anhydride and then refluxed under stirring for 16 hours. The reaction mixture was cooled to room temperature and then 400 ml of anhydrous ether was added thereto. The reaction mixture was stirred for 1 hour, filtered with Celite, and then concentrated under reduced pressure to give 4-acetoxy-2,3-dimethylpyridine (45 g, 91%). The resulting residue was added to 250 ml of water, refluxed under stirring for 4 hours, and then left overnight at room temperature. The reaction mixture was concentrated under EPO reduced pressure to give 32.6 g of 2,3-dimethyl-4-hydroxypyridine as a liquid form. The liquid product was dissolved in 120 ml of concentrated sulfuric acid and heated to 60⁰C. A mixture of 90% nitric acid (40 ml) and sulfuric acid (30 ml) was slowly added to the reaction mixture for 45 minutes, while maintaining the temperature at 60-65⁰C. The reaction mixture was heated for 2 hours at 65°C and then for 30 minutes at 75°C. The reaction mixture was cooled to room temperature and then added to ice water. The resulting solution was brought to pH 5-6 with ammonium hydroxide to give a pale yellow solid. The resulting solid was filtered, washed with cold water, and then dried at 80 ~ 90⁰C to give 34.5 g of the titled compound.[757] * H-NMR (CDCl₃) δ 2.54(s, 3H), 2.87(s, 3H), 9.35(s, IH)

References:

WO2006/38773,2006,A1 Location in patent:Page/Page column 54-55