2-Bromo-4-methyl-5-nitropyridine

2-Bromo-4-methyl-5-nitropyridine (104 g, 0.479 mol), Zn(CN)2 (79 g, 0.673 mol, 1.4 eq. ), and Pd (PPh3)4 0.023 mol, 5 mol%) were added to a round bottom flask. NOTE: Using catalyst purchased from STREM resulted in shorter reaction times and better yields. DMF (900 mL) was degassed for 10 min before adding to the solid mixture. The mixture was heated in an oil bath to an inside temp of 80 C. The color changed from light yellow to light brown as the inside temperature reached 80 C. The mixture was stirred at the same temperature for 3 h, and monitored by TLC. The solvent was removed in vacuo. The residue was dissolved in a mixture of dichloromethane and water, and insoluble material was removed by filtration through Celite. The organic layer was separated and the aqueous layer was extracted with dichloromethane. The combined organic extracts were dried (magnesium sulfate), and concentrated. The residue was purified by column chromatography starting with 100% hexanes to hexanes/ethyl acetate 4: 1. Recrystallization from hexanes yielded 65.8 g (83%) of the desired product. ¹H NMR (300 MHz, CDC13) 8 ppm 2.71 (s, 3 H) 7.73 (s, 1 H) 9.20 (s, 1 H). LCMS: APCI, M-H-) = 162 u/e Purity by TIC: 95 %; Purity by UV: 95 %.To a solution of A solution of 4-methyl-5-nitropyridin-2-ol (82 g, 0.53 mol) and POBr3 (229 g, 0.8 mol, 1.5 eq. ) in dichloromethane (2 L) was heated under a nitrogen atmosphere in a 3 L 3-neck flask with overhead stirrer for 24 h. The mixture was filtered cold. The solid consisted of a 1: 1 mixture of desired product 2 and unreacted starting material 4-methyl-5- nitropyridin-2-ol, the filtrate contained the desired product and unreacted POBr3. The solid (46 g) and fresh POBr3 were dissolved in dichloromethane and refluxed for 10 h. The liquid was decanted and combined with the filtrate of the first reaction. The combined solutions were concentrated to a volume of 1.5 L. The mixture was cooled in an ice bath and stirred while ice (500 g) was added to quench the excess POBr3. The organic layer was separated, and the aqueous layer was extracted with dichloromethane. The combined organic extracts were dried (magnesium sulfate) and concentrated. The product was recrystallized from hexanes. Yield: 104 g (90%). ¹H NMR (300 MHz, CDC13) No. ppm 2.63 (s, 3 H) 7.52 (s, 1 H) 8.95 (s, 1 H). LCMS: (APCI, M-H') = 215 and 217 u/e (bromine isotope pattern) ; Retention Time: 3.01 min; Purity by TIC: 95%; Purity by UV: 95%.To a suspension OF 2-HYDROXY-4-METHYL-5-NITROPYRIDINE (LG, 6. 5MMOL) in dichloroethane (lOmL) was added a solution of phosphorus oxybromide (2.8g, 9.7mmol) in dichloroethane (LOML). The reaction mixture was heated under reflux for 4h, then cooled to rt and quenched with water (40mL). The layers were separated and the aqueous layer extracted into dichloromethane (2 x 30mL). The combined organics were dried (MGS04), concentrated IRA vacuo and chromatographed on silica gel eluting with dichloromethane to give the title compound as a pale yellow SOLID. 8H (CDCl3): 2.63 (3H, s), 7.52 (1H, s), 8.96 (1H, s).To a solution of

Molecular Weight:217.02
XLogP3:2.1
Hydrogen Bond Acceptor Count:3
Exact Mass:215.95344
Monoisotopic Mass:215.95344
Topological Polar Surface Area:58.7
Heavy Atom Count:11
Complexity:159
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes