Yield: 74%

Reaction Conditions:

Stage #1:2-methoxy-3-(trifluoromethyl)pyridine with 1,3-dibromo-5,5-dimethylimidazolidine-2,4-dione;trifluoroacetic acid at 20; for 18 h;Inert atmosphere;
Stage #2: with sodium hydrogencarbonate in n-heptane;ethyl acetate

Steps:

Intermediate 1 : 5-Bromo-2-methoxy-3-trifluoromethyl-pyridine To 2-methoxy-3-(trifluoromethyl)pyridine (20.0 g, 1 13.0 mmol) and 1 ,3-dibromo-5,5- dimethylimidazolidine-2,4-dione (43.6 g, 152.0 mmol) was added TFA (80 mL) and the resulting mixture stirred at rt for 18h under argon. The TFA was removed in vacuo (50 mbar, 45°C) and the residue suspended in tert-butyl methyl ether (200 mL). The resulting colourless solid was removed by filtration and washed with tert-butyl methyl ether (50 mL). The filtrate was concentrated in vacuo and suspended in EtOAc (50 mL) The insoluble colourless solid was removed by filtration and washed with EtOAc (50 mL).The filtrate was concentrated in vacuo, diluted with heptane/ tert-butyl methyl ether (5/1 , 20 mL) and the insoluble colourless solid was removed by filtration. The filtrate was purified by column chromatography on silica gel with heptane / EtOAc, 100/0 to 90/10. The crude product was filtered through a plug of NaHC0₃ (20g) and the filtrate evaporated in vacuo to give a golden oil (27.9 g). The oil was dissolved in heptanes (20 mL) and purified by filtered through a plug of silica gel (80 g), eluting with heptane to give 5-bromo-2-methoxy-3-(trifluoromethyl)pyridine as a colourless oil (22.5g, 74% yield). ¹ H-NMR (400 MHz, DMSO-d_6, 298 K): δ ppm 4.03 (s, 3H) 7.95 (d, 1 H) 8.4 (d, 1 H).

References:

NOVARTIS AG;COOKE, Nigel Graham;FERNANDES GOMES DOS SANTOS, Paulo;GRAVELEAU, Nadege;HEBACH, Christina;H?GENAUER, Klemens;HOLLINGWORTH, Gregory;SMITH, Alexander Baxter;SOLDERMANN, Nicolas;STOWASSER, Frank;STRANG, Ross;TUFILLI, Nicola;VON MATT, Anette;WOLF, Romain;ZECRI, Frédéric WO2012/4299, 2012, A1 Location in patent:Page/Page column 66-67