1-Benzyloxy-3-bromobenzene

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To a suspension of m-bromophenol (1) (15.57 g, 90 mmol) in dehydrated alcohol (300 mL) was added anhydrous potassium carbonate (37.32 g, 270 mmol) and benzyl chloride (11.50 mL, 99 mmol). The mixture was refluxed for 4 h. Filtration and evaporation of alcohol was done in a vacuum. The residue was extracted with EtOAc. The combined organic layers were washed with water, NaOH (2 M), brine, and HCl (2 M), dried over Na(1) 0.77 g of benzyl chloride was dropwise added to a mixed solution comprising 1.0 g of 3-bromophenol, 1.6 g of potassium carbonate and 5 mL of N, N- dimethylformamide. After completion of the dropwise addition, a reaction was carried out at 60°C for 2 hours. Water was added to the reaction solution, followed by extraction with ethyl acetate. Then, the organic layer was washed with water and an aqueous sodium chloride solution, and anhydrous sodium sulfate was added for drying. The solvent was distilled off under reduced pressure to obtain 1.6 g of oily 1 - (benzyloxy)-3-brornobenzene.A solution of 3-bromophenol (3 g, 17.34 mmol) in acetone (100 mL) was added with benzyl bromide (2.2 mL, 19.07 mmol) and KExample 81 3- {2-Methyl-4- [3- (2-phenoxy-4-trifluoromethyl-phenoxy)-phenoxy]-phenyl}-propionic acid Step A 3-Benzyloxy-1-bromobenzene A mixture of 3-bromophenol (10. 0 g, 57.8 mmol) and 325 mesh potassium carbonate (8.79 g, 63.6 mmol) in DMF (100 mL) is treated dropwise with benzyl bromide (9.89 g, 57.8 mmol) and then stirred 20 hours at rt under N2. The reaction is filtered, and the filtrate is acidified with 1 N HCI. The mixture is then diluted with water and extracted with Et20. The organic layer is dried (Na2S04), and the solvent is removed in vacuo to afford crude product that is absorbed on silica gel and purified by flash chromatography using 10/1 hexanes/ethyl acetate to afford 14.55 g (96percent) of the titled compound. Rf= 0.86 (4/1 hexanes/EtOAc). IH NMR (400 MHz, CDC13).Step-1: Synthesis of l-(benzyloxy)-3-bromobenzene BnBr/K4.6.2.19 3-(3-Benzyloxy-phenyl)-3-(3, 5-dimethoxy-phenyl)-acrylonitrile 4.6.2.95 (E/Z)-3-(3, 5-Dimethoxy-phenyl)-3-(3-ethoxy-phenyl)-acrylonitrile 4.6.2.96 Z-3-(3, 5-Dimethoxy-phenyl)-3-(3-hydroxy-phenyl)-acrylonitrile REFERENCE Intermediate 21 : 1-(benzyloxy)-3-bromobenzene A mixture of 3-bromophenol (2.60 g, 1.59 mL, 15 mmol), benzyl bromide (2.82 g 1.96 mL, 16.5 mmol) and potassium carbonate (2.07 g, 15 mmol) in acetone (25 mL) was refluxed for 4 hours. The reaction mixture was cooled to room temperature. The mixture was filtered and the solvent was evaporated from the filtrate. The residue was purified by chromatography on silica gel eluting with 0- 25 percent ethyl acetate/hexane. Appropriate fractions were combined and evaporated. The impure product was re-purified by chromatography on silica gel eluting with 0-10 percent ethyl acetate/hexane to give 1-(benzyloxy)-3-bromobenzene (2.25 g, 8.55 mmol, 57.0 percent yield) as a white solid. 1H NMR (400MHz, DMSO-dTo a mixture of 3-bromophenol (20 g, 0.115 mol) and potassium carbonate (95 g, 0.69 mol, 6 eq) in acetone (500 ml) was added benzyl bromide (15.12 ml, 0.127 mol, 1.1 eq). The reaction mixture was heated at reflux for 2 hours (TLC showed completion of reaction). The reaction mixture was filtered, washed with acetone and the filtrate was evaporated to dryness. The residue was dissolved in water (200 ml) and ethyl acetate (200 ml). The layers were separated. The organic layer was washed with brine (200 ml), dried over sodium sulfate, filtered and evaporated to dryness. The crude was recrystallized from hexane to give the title compound (26 g) 3 as a white solid. MP 61-62° C.

Molecular Weight:263.13
XLogP3:4.5
Hydrogen Bond Acceptor Count:1
Rotatable Bond Count:3
Exact Mass:261.99933
Monoisotopic Mass:261.99933
Topological Polar Surface Area:9.2
Heavy Atom Count:15
Complexity:177
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes