1-Benzyloxy-4-bromo-2,5-difluorobenzene synthesis

Yield:901238-24-2 88%

Reaction Conditions:

Stage #1: 4-bromo-2,5-difluoro phenolwith caesium carbonate in N,N-dimethyl-formamide; for 0.25 h;
Stage #2: benzyl bromide in N,N-dimethyl-formamide at 20; for 1 h;

Steps:

22.a

Description 22. 1-{2,5-difluoro-4-[(phenylmethyl)oxy]phenyl}-4- [(phenylmethyl)oxy]-1 H-indole (D22) a) 4-bromo-2,5-difluorophenol (2 g, 9.57 mmol) was dissolved in DMF (19 ml.) and to this was added Cs₂CO₃ (4.37 g, 13.34 mmol) and the solution was stirred for 15 minutes before benzyl bromide (1.64 g, 9.57 mmol) was added. After 1 hour at room temperature the mixture was partitioned between ethyl acetate (100 ml_)/water (100 ml_), the layers were separated and the aqueous extracted with ethyl acetate. The combined organics were washed with saturated NH₄CI (100 ml_), water (100 mL) and brine (2x100 mL) and dried over MgSO₄. The crude material (2.74 g) was filtered through a pad of silica and eluted with 20% Et₂O in hexane to afford 4-bromo-2,5- difluorophenyl phenylmethyl ether after evaporation of the solvent (2.51 g, 88%). NMR (δ_H), (CDCI₃): 7.3-7.45 (5 H, m), 7.25-7.29 (1 H, dd), 6.78-6.82 (1 H, dd), 5.1 (2H, s).

References:

WO2009/103710,2009,A1 Location in patent:Page/Page column 24; 25