ethyl 5-aMino-6-broMo-2-Methylnicotinate synthesis

Yield:1149388-64-6 88%

Reaction Conditions:

with N-Bromosuccinimide in N,N-dimethyl-formamide at 20;

Steps:

49.1

STEP 1 : To a solution of ethyl 5-amino-2-methylnicotinate (Fanta, P. E. J. Am. Chem Soc. 1953, 75, 737) (4.1 g, 22.78 mmol) in DMF (50 ml) was added NBS (4.46 g, 25.06 mmol), and the reaction mixture was stirred at room temperature overnight. The reaction mixture was diluted with water (100 ml) and then extracted with ethyl acetate (3x 100 ml). The organic layer was washed with saturated aqueous sodium bicarbonate and brine. After evaporation of solvent, the residue was triturated with ethanol to give ethyl 5-amino-6-bromo-2-methylnicotinate (5.2 g, 88% yield). 1H NMR (400 MHz, CDCl₃): 7.56 (s, IH), 4.40 (q, J = 6.8 Hz, 2H), 4.05 (br, s, 2H), 2.75 (s, 3H), 1.39(t, J = 6.8Hz, 3H). MS (EI) for C₉H₁₁BrN₂O₂: 259.1 (MH⁺).

References:

WO2009/55077,2009,A1 Location in patent:Page/Page column 454