3-bromo-5-methoxy-4-methylpyridine synthesis

Yield:-

Reaction Conditions:

in methanol;N,N-dimethyl-formamide at 80;

Steps:

To a freshly prepared sodium methoxide from sodium metal (0.165 g, 0.0072 mol) and methanol (2.5 mL), 3,5-dibromo-4-methyl-pyridine (1.0 g, 0.0040 mol) dissolved in N,N-dimethylformamide (10 mL) was added and heated at 80 °C overnight Reaction was diluted with ethyl acetate and quenched with ice water, and layers were separated. The aqueous layer was extracted with ethyl acetate (3 x 20 mL). The combined organic extracts were washed with saturated aqueous sodium chloride solution, dried over sodium sulphate and concentrated to provide the title compound. 1H NMR (400 MHz, CDC1₃) δ 8.33 (s, 1 H), 8.09 (s, 1 H), 3.05 (s, 3 H), 2.32 (s, 3 H).

References:

MERCK SHARP & DOHME CORP.;ElexoPharm GmbH;HOYT, Scott, B.;PETRILLI, Whitney Lane;LONDON, Clare;XIONG, Yusheng;TAYLOR, Jerry Andrew;ALI, Amjad;LO, Michael;HENDERSON, Timothy, J.;HU, Qingzhong;HARTMANN, Rolf;YIN, Lina;HEIM, Ralf;BEY, Emmanuel;SAXENA, Rohit;SAMANTA, Swapan Kumar;KULKARNI, Bheemashankar, A. WO2012/148808, 2012, A1 Location in patent:Page/Page column 47; 48