1-BROMO-4-ETHOXY-2-FLUORO-5-METHOXYBENZENE synthesis

Yield: 95%

Reaction Conditions:

with sodium hydride in N,N-dimethyl-formamide at 20; for 16 h;

Steps:

l-Bromo-4-ethoxy-2-fluoro-5-methoxybenzene To a slurry of 4-bromo-5-fluoro-2-methoxyphenol (2.00 g, 9.05 mmol) and sodium hydride(0.543 g, 13.6 mmol) in DMF (9.05 mL) was added ethyl iodide (1.45 mL, 18.1 mmol) and the reaction stirred at ambient temperature for 16 hours. The reaction mixture was quenched with water (5 mL), diluted with EtOAc (50 mL) and washed sequentially with 2M NaOH (25 mL) and saturated brine (50 mL). The organic layer was dried over MgSO₄, filtered and evaporated to afford desired product l-bromo-4-ethoxy-2-fiuoro-5- methoxybenzene (2.15 g, 95 %) as a brown solid.MS (+ve ESI) : Rt = 2.49 min, no mass ion (M+H)⁺¹U NMR (400.13 MHz, CDC13) δ 1.47 (3H, t), 3.84 (3H, s), 4.05 (2H, q), 6.68 - 6.71 (IH, m), 6.96 (IH, d)

References:

ASTRAZENECA AB;ASTRAZENECA UK LIMITED WO2009/1127, 2008, A1 Location in patent:Page/Page column 267-268