4-(BENZYLOXY)-PHENACYLBROMIDE

To a clear solution of 1-(4-(benzyloxy)phenyl)-2-bromoethanone To a clear solution of l-(4-(benzyloxy)phenyl)ethanone (16.1 g, 71.2 mmol) in tetrahydrofuran (200 mL) was added dropwise a solution of phenyltrimethylammonium tribromide (29.4 g, 78 mmol) in tetrahydrofuran (150 mL) at 0°C. After completion of the reaction, the insoluble material was filtered off and washed with tetrahydrofuran. The filtrate was evaporated and the yellow oil was crystallized from isopropanol. (Yield: 17.99 g, 83percent).Pyridinium tribromide (9.5 g, 29.8 mmol) was added to a solution of 4-benzyloxy- acetophenone (6.1 g, 27.1 mmol) in CH2CI2 (275 mL) and MeOH (100 mL) at rt. After 3 h at rt the mixture was concentrated and the residue partitioned between water and EtOAc.The layers were separated and the aqueous layer was extracted with EtOAc. The combined organic phases were washed with brine, dried over Na2SO4 and filtered. Concentration of the filtrate and crystallization of the residue from hexane/EtOAc gave the sub-title compound (6.4 g, 21.1 mmol, 78 percent).A solution of tetrabutylammonium tribromide (53g, 110mm) in tetrahydrofuran (70mL) was added dropwise to a suspension of 4-benzyloxyacetophenone (27.38g, 121mmol) in tetrahydrofuran (100mL) and methanol (25mL) over 1 hour. The reaction mixture was then left to stir for 48 hours and the solvent removed in vacuo. The residue was dissolved in ethyl acetate (250mL) and washed with water (250mL). The phases were separated and the aqueous layer was extracted with ethyl acetate (2 x 100mL). The organic layers were combined, dried over magnesium sulfate and concentrated in vacuo to give a solid. The crude residue was recrystallised using cyclohexane to afford the desired product, 22g (65percent). 1H NMR (400 MHz, CDCI3) 6 4.38 (2H, s), 5.10 (2H, s), 7.00 (2H, m), 7.21-7. 40 (5H, m), 7.9 (2H, m). LRMS: m/z APCI+ 305 [MH+].(2) Step 2: Synthesis of l-(4-(benzyloxy)phenyl)-2-bromoethan-l-one: [0247] To the stirred solution of l-(4-(benzyloxy)phenyl)ethan-l-one (step 1, 25 g, 110.5 mmol) in 200 ml of MeOH at 0°C was added Bromine (4.5 ml, 28.5 mmol) (dropwise addition), stirred for about 30 minutes and stirred for about 4 hours at room temperature. After completion of the reaction (monitored by TLC), the reaction mixture was concentrated and the crude product was dissolved in n-hexane and stirred for about 30 minutes. The obtained solid was filtered and washed with n-hexane then dried and proceeded for next step (wt: 16.0g). M.Wt: 305.Step 1: Preparation of l-(4-(benzyloxy)phenyl)-2-bromoethanone [00170] To a solution of 2-bromo- 1 -(4-hydroxyphenyl)ethanone (2 g, 9.3 mmol) in tetrahydrofuran (70 mL) was added silver carbonate (5.128 g, 18.6 mmol) and the reaction mixture was cooled to 0 °C. Benzyl bromide (1.32 m L, 11.16 mmol) was added drop wise and the reaction mixture was stirred at room temperature for 16 h. The reaction mixture was filtered through celite, the filtrate was diluted with ethyl acetate (200 mL) and washed with water (60 mL x 2). The organic layer was dried over anhydrous sodium sulfate, filtered and concentrated. The crude was purified by column chromatography using 6percent ethyl acetate in hexane to afford title l-(4-(benzyloxy)phenyl)-2-bromoethanone (1.22 g, 43percent yield) as a white solid. Calculated M+H: 306.17; Found M+H: 306.

Molecular Weight:305.17
XLogP3:4.3
Hydrogen Bond Acceptor Count:2
Rotatable Bond Count:5
Exact Mass:304.00989
Monoisotopic Mass:304.00989
Topological Polar Surface Area:26.3
Heavy Atom Count:18
Complexity:253
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes