1-Bromo-4-phenyl-2-Butanone

To a stirred solution of 4-phenylbutan-2-one (4) (50 g, 1 mmol) in methanol (350 mL), bromine (19 mL, 1.1mmol) was added at 0°C and the mixture was stirredat 15°C for 4 h. After completion of reaction, the reactionmixture was diluted with water (500 mL) andextracted with dichloromethane (2 x 500 mL). The collectedorganic layer was washed with brine solution and dried over anhydrous Na2SO4 and concentrated underreduced pressure. The residue was dissolved in pet etherand kept in refrigerator for 5 h. The solid was filtered toafford compound 5 as a white solid (72 g, 93.98percent). 1HNMR (300 MHz, CDCl3): δ2.9 (q, 4H), 3.8 (s, 2H), 7.2(m, 3H), 7.3 (m, 2H). 13C NMR (100 MHz, CDCl3):δ29.87, 34.24, 41.38, 126.34 (2C), 128.28 (2C), 128.57, 140.29, 201.18.4-Phenylbutan-2-one (10 g, 67.5 mmol, 1 eq) as starting material was added to a 100 ml 3-neck flask and 40 ml of MeOH was added. AcOH (4 ml, 67.5 mmol, 1 eq) was slowly added and stirred for 10 min. After cooling to-5 ° C, Br2 (4 ml, 78.3 mmol) was dissolved in 20 ml of MeOH and then slowly added dropwise. After raising the temperature to 15 to 20 , the mixture was stirred for 2 hours. After cooling to 5 , 50 ml of H 2 O was added, and the mixture was stirred for 10 minutes. After layer separation, 20 ml of hexane was added to the organic layer, cooled to 0 and stirred for 30 minutes. The resulting solid was filtered to give a white solid compound (9.9 g, 65percent)1.1) To a solution of 4-phenylbutan-2-one (20) (3.0 g) in AcOH(7 mL) and 48percent aqueous HBr (3 mL) was added a solution of Br2(6.5 g) in AcOH (5 mL) at 0 C. After stirring the reaction mixtureat room temperature for 4 h, acetone (30 mL) was added to thesolution, and the reaction mixture was further stirred at room temperaturefor 14 h. The mixture was then concentrated in vacuo, dilutedwith brine, and extracted twice with CH2Cl2. The combinedorganic layer was dried over anhydrous MgSO4, and then evaporatedin vacuo. The obtained residue was purified by flash columnchromatography over silica gel with hexane/AcOEt (40:1–10:1) asan eluent to give 21 (1.5 g, 34percent) as a pale brown oil. CI MS m/e (M)+227.To a solution of ketone 1 (4.52g, 30mmol) 240ml in methanol, a solution of bromine (1.5ml), 30mmol) in 30ml methanol was added in one portion at room temperature. The orange reaction mixture was then stirred at room temperature for 2 h. After the ketone 1 has been consumed, the reaction was quenched by adding a 0.3M sodium thiosulfate solution(18ml) and diluted with EA (450ml). The resulting mixture was washed with 450ml water, then the organic phase was concentrated under reduce pressure to give a residue that was purified by chromatography (PE/EA, 10/1) to give the compound 2 (1.43g, 21percent). General procedure: The reaction mixture of In(OTf)General procedure: Oxalyl chloride (23 mmol) was added dropwise to a solution of the appropriate phenylalkyl acid (1a-f) (10 mmol) in dry CH(i) A soln of 3-phenyl-propionyl chloride (2.0 mL; 13.5 mmol) in dry THF (50 mL) was added over 6 min to a 0 °C soln of diazomethyl-trimethyl-silane (2.0 M in hexanes; 15 mL; 30 mmol) in dry THF (50 mL). After 3 h, the rxn was coned to a liquid, (ii) Aq. HBr (48percent; ca. 2.5 eq) was added in one portion to a soln of this crude material in AcOH (30 mL) at 0 °C. After 10 min the rxn was coned. EtOAc (50 mL) was added and the soln washed with water (2 x 15 mL), satd NaHCO3 (3 x 15 mL), water (1 x 15 mL) and satd NaCl (2 x 15 mL). After drying over MgSO4, filtering through a pad of silica with an EtOAc wash and coned to an oil, the crude material was purified by MPLC (SiO2 with a 0 - > 20percent EtOAc in hexanes gradient) yielding bromomethyl ketone as an off-white solid (1.977 g; 65percent). IH NMR (CDC13) δ 7.37 - 7.18 (m, 5H), 3.85 (s, 2H), 3.01 - 2.94 (m, 4H); GC-MS 226/228 ([M]+).General procedure: Oxone (1.352 g, 2.2 mmol) was added to the well stirred solution of substrate (2 mmol) and NHStep B: Preparation of General procedure: A sealed tube (35 mL) equipped with a stirring bar was loaded with 2-bromoethanones (1.0 mmol), then sodium benzenesulfinate (1.2 mmol) in DMF (20 mL) or phosphite (1.0 mmol) in toluene (20 mL) was added to the tube and the mixtures were stirred at room temperature till the 2-bromoethanones was totally consumed as indicated by TLC analysis (ca. 12 h for 1 and 24 h for 3). Then, the mixture was diluted with water (20 mL) and extracted with CH2Cl2 (30 mL x 3). Next, the organic phase was combined and dried over anhydrous Na2SO4. The solvent was removed by rotary evaporation and the oily mixture was purified with flash chromatograph column (elute: mixture of ethyl acetate and n-hexane), giving the desired products. And the 1H NMR spectra of the purified substrates were in accordance with the known literatures.

Molecular Weight:227.10
XLogP3:2.6
Hydrogen Bond Acceptor Count:1
Rotatable Bond Count:4
Exact Mass:225.99933
Monoisotopic Mass:225.99933
Topological Polar Surface Area:17.1
Heavy Atom Count:12
Complexity:139
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes