2,5-Dibromo-3-methylpyridine synthesis
- Product Name:2,5-Dibromo-3-methylpyridine
- CAS Number:3430-18-0
- Molecular formula:C6H5Br2N
- Molecular Weight:250.92
3430-21-5
3430-18-0
General procedure for the synthesis of 2,5-dibromo-3-methylpyridine (49) from 2-amino-3-methyl-5-bromopyridine (48, 69 g, 0.37 mol): the raw material was suspended in hydrobromic acid (200 mL, 48% aqueous solution) and cooled to -15 °C. The reaction was carried out in aqueous solution of sodium nitrite (100 mL). Bromine (95 g, 0.59 mol) was slowly added dropwise, followed by an aqueous solution (100 mL) of sodium nitrite (69 g, 1 mol), while keeping the temperature of the reaction mixture below -15 °C. The reaction mixture was then cooled to -15 °C. After completion of the dropwise addition, the cooling bath was removed and the reaction mixture was stirred for 3 hours at room temperature. The reaction was cooled again to -15 °C and quenched with an aqueous solution (500 mL) of potassium hydroxide (112 g, 2 mol). After removing the cooling bath, stirring was continued for 1.5 hours. The product was extracted with ethyl acetate (3 x 300 mL), the organic phases were combined, washed sequentially with water (2 x 200 mL), saturated aqueous sodium bicarbonate (200 mL), dried over sodium sulfate and concentrated to dryness under reduced pressure. The oily residue was dissolved in chloroform (100 mL), filtered through a silica gel pad and washed with chloroform. The filtrates were combined and evaporated under reduced pressure to give the light yellow solid product 49 (87 g, 94%) with a melting point of 38-40 °C (literature value: 41-42 °C). The structure of the product was confirmed by 1H NMR (300 MHz, CDCl3) δ 8.22 (d, J = 2.4 Hz, 1H), 7.61 (d, J = 2.4 Hz, 1H), 2.33 (s, 3H); 13C NMR (75 MHz, CDCl3) δ 148.29, 143.05, 141.15, 137.15, 119.68, 22.06 Confirmed.
3430-21-5
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3430-18-0
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Yield:3430-18-0 94%
Reaction Conditions:
with hydrogen bromide;bromine;sodium nitrite in water at -15 - 23; for 3 h;
Steps:
2,5-Dibromo-3-methylpyridine (49)
2,5-Dibromo-3-methylpyridine (49) [0175] (J. Med. Chem. 2007, 50, 3730-3742.) 5-Bromo-3-methylpyridin-2-amine (48, 69 g, 0.37 mol) was suspended in hydrobromic acid (200 mL, 48% in water), and the mixture was cooled to -15° C. Bromine (95 g, 0.59 mol) was added dropwise to the mixture, followed by addition of sodium nitrite (69 g, 1 mol) in water (100 mL). Temperature of the reaction mixture was kept below -15° C. during addition. After addition, the cooling bath was removed and the reaction mixture was stirred for 3 h. The reaction mixture was cooled to -15° C. and quenched with potassium hydroxide (112 g, 2 mol) in water (500 mL). The cooling bath was removed, and the mixture was stirred for 1.5 h. The products were extracted with ethyl acetate (3×300 mL). The combined extracts were washed with water (2×200 mL), saturated aqueous sodium bicarbonate (200 mL), dried with sodium sulfate, and evaporated to dryness. The oily residue was redissolved in chloroform (100 mL), and the solution was filtered through a pad of silica gel, washing with chloroform. The combined filtrates were evaporated to provide 49 as light-yellow solid (87 g, 94%): mp 38-40° C. (lit. (Recl. Tray. Chim. Pays-Bas 1965, 84, 951-964) mp 41-42° C.). 1H NMR (300 MHz, CDCl3) δ 8.22 (d, J=2.4 Hz, 1H), 7.61 (d, J=2.4 Hz, 1H), 2.33 (s, 3H); 13C NMR (75 MHz, CDCl3) δ 148.29, 143.05, 141.15, 137.15, 119.68, 22.06.
References:
CUSHMAN, Mark S.;KISELEV, Evgeny A.;MORRELL, Andrew E. US2014/18360, 2014, A1 Location in patent:Paragraph 0175
1603-40-3
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3430-18-0
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