2,5-DIBROMO-6-METHYLPYRIDINE

white to light yellow solid

To a solution of 2-amino-5-bromo-6-methylpyridine (37.6 g, 200 mmol) in aqueous HBr (48percent, 200 mL), cooled at 0 6-Amino-3-bromo-2-methylpyridine (25.0 g, 134 mmol) was dissolved in 150 ml of 48percent HBr solution. Sodium nitrite (11.04 g, 160 mmol) was dissolved in 25 ml water and added dropwise at room temperature and stirred over night. The reaction was diluted with 200 ml of water and extracted three times with 100 ml of ethyl acetate. The combined organic layers were washed three times with 100 ml of 1 N HCI solution, dried over MgSO4, filtered and evaporated. The resulting solid was stirred in 250 ml of diethyl ether and filtered. The ether filtrate was evaporated to give a solid (4.61 g, 14percent yield). 1H NMR (400 MHz, DMF-d7) δ 7.97 (d, J= 8.3 Hz, 1 H), 7.47 (app dd, J = 8.3, 0.5 Hz, 1 H), 2.57 (s, 3H); LC/MS, tr = 2.53 minutes (5 to 95percent acetonitrile/water over 5 minutes at 1 ml/min, at 254 nm, at 50 0C), ES-MS m/z 250 (M+H).6-Amino-3-bromo-2-methylpyridine (25.0 g, 134 mmol) was dissolved in 150 ml of48percent HBr solution. Sodium nitrite (11.04 g, 160 mmol) was dissolved in 25 ml water and addeddropwise at room temperature and stirred over night. The reaction was diluted with 200 ml ofwater and extracted three times with 100 ml of ethyl acetate. The combined organic layers werewashed three times with 100 ml of 1N HCI solution, dried over MgSO5-Bromo-2-amino-6-picoline hydrobromide (29.4 kg, 76.5 wgt percent purity, 84 mol, 1.00 eq) was dissolved into 48percent hydrobromic acid (162.0 kg, 961 mol, 11.44 eq) at <35 °C. The solution was cooled to 2 °C and bromine (43.0 kg, 269 mol, 3.20 eq) was charged over 40 min. A 40 wt percent solution of sodium nitrite (28.9 kg, 419 mol, 4.99 eq) was charged over 50 min at -1 to 5 °C. The contents were held one hour and the pH was adjusted to 13.1 using 50percent aqueous sodium hydroxide (120.0 kg). The contents were warmed to 20 °C over one hour and toluene (78.0 kg) was charged. The mixture was stirred for 30 min and allowed to settle overnight. The organic phase was clarified by filtration and washed twice with saturated aqueous sodium chloride solution (51.1 kg). This produced 96.0 kg of 2, 5-dibromo-6-picoline solution (17.3 wgt percent) or 79percent yield.5-Bromo-2-amino-6-picoline (7.0 kg) and 5-bromo-2-amino-6-picolinehydrobromide (7.0 kg) (based on the starting material analyses, this was equal to 11 kg or 41 mol of starting material) are dissolved into 48percent hydrobromic acid (107.0 kg, 635 mol, 15.49 eq) at <35 °C. The solution was cooled to 2 °C and bromine (27.3 kg, 171 mol, 4.17 eq) was charged over 45 min at 0-5 °C. A solution of sodium nitrite (8.1 kg, 117 mol, 2.86 eq) in 20 L of water was charged over 1.5 hours at -1 to 5 °C. The contents were held one hour and the pH was adjusted to 12.5 using 50percent aqueous sodium hydroxide (70.0 kg). The contents were warmed to 20 °C over one hour and the solids were collected in a polypropylene bag on a centrifuge. The solids were washed with water (75 L) to produce 12.0 kg of moist 2, 5-dibromo-6-picoline, determined to be 83 wgt percent product (68 percent yield). Part of this was dried for the purposes of recording the

Molecular Weight:250.92
XLogP3:3
Hydrogen Bond Acceptor Count:1
Exact Mass:250.87682
Monoisotopic Mass:248.87887
Topological Polar Surface Area:12.9
Heavy Atom Count:9
Complexity:97.1
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes