1-(2-broMo-1-fluoroethyl)benzene

The reaction was performed in a plastic vial. A mixture of NBS (53.4 mg, 0.3 mmol) and alkene (0.20 mmol) in CHTriethylamine trihydrofluoride (36.3 mL, 216.01 mmol) and N-bromosuccinimide (30.75 g, 172.8 mmol) was added to a solution of styrene (15 g, 144.0 mmol) in DCM (150 mL) at 0 °C and stirred at RT for 16 h. After completion, the reaction mixture was neutralized with aq NH4OH solution (150 mL) and extracted with DCM (2 x 200 mL). The combined extracts were washed with 0.1 N HCI solution (100 mL), 5 percent NaHCO., solution (100 mL), brine (100 mL) and dried over anhydrous a2S04, filtered and concentrated to afford (2-bromo-1- fluoroethyl) benzene (25 g, 85 percent) as a brown liquid.According to the general procedure, in the reaction of fluorinating agent PFPDEA (0.926 g, 5.0 mmol), HGeneral procedure: In an ordinary glassware round-bottom flask to a solution of PFP-DA (5 equiv.) in dry CH2Cl2 (1.5 mL) at room temperature, water (5 equiv.) was added. Forthwith the hydrolysis occurred, the resulting mixture was placed in cooling bath (acetonitrile/dry ice). To the cooled reaction mixture ( 30 8C) NXS or DBH (2.5 equiv.) and HMPA (2.0 equiv.) were added, and the whole was stirred at the temperature for next 30 min. A solution of alkene (1 equiv.) in CH2Cl2 (1.5 mL) was added dropwise, cooling bath was removed and the reaction mixture was allowed to stand at room temperature for 24 h. When the reaction was complete the appropriate amount of NMR internal standard, m-fluorotoluene (1 equiv.), was added and a sample analyzed by NMR.The reaction was performed in a plastic vial. A mixture of NBS (53.4 mg, 0.3 mmol) and alkene (0.20 mmol) in CH2Cl2 (1 mL) was treated with DMPU/HF (41.2 muL, 1.4 mmol) and stirred for 24 h at room temperature. Next, water (2 mL) was added and the resultant mixture was extracted with CH2Cl2 (3 × 2 mL). The organic layer was dried over Na2SO4 and concentrated under reduced pressure. SiO2 flash chromatography (9:1 hexanes/EtOAc) afforded the bromofluoride compounds as mixtures of regioisomers in some cases. (2-bromo-1-fluoroethyl)benzene (2a). 1H NMR (400 MHz, CDCl3) delta 7.50 (m, 5H), 5.60 (dd, J =47.1, 7.8, 4.1 Hz, 1H), 3.66 (ddd, J = 15.3, 11.3, 7.8 Hz, 1H), 3.58 (ddd, J = 26.0, 11.3, 4.2 Hz, 1H), 19F NMR (376 MHz, CDCl3) delta -175.0 (m), Colorless oil.Triethylamine trihydrofluoride (36.3 mL, 216.01 mmol) and N-bromosuccinimide (30.75 g, 172.8 mmol) was added to a solution of styrene (15 g, 144.0 mmol) in DCM (150 mL) at 0 C and stirred at RT for 16 h. After completion, the reaction mixture was neutralized with aq NH4OH solution (150 mL) and extracted with DCM (2 x 200 mL). The combined extracts were washed with 0.1 N HCI solution (100 mL), 5 % NaHCO., solution (100 mL), brine (100 mL) and dried over anhydrous a2S04, filtered and concentrated to afford (2-bromo-1- fluoroethyl) benzene (25 g, 85 %) as a brown liquid.According to the general procedure, in the reaction of fluorinating agent PFPDEA (0.926 g, 5.0 mmol), H2O (0.009 g, 9.0 muL, 5.0 mmol), DBH (0.715 g, 2.5 mmol), HMPA (0.358 g, 0.35 mL, 2.0 mmol) and styrene (0.104 g, 0.115 mL, 1.0 mmol) in dry CH2Cl2 3a was obtained. The NMR data were in a good agreement with those already reported [7-9].General procedure: In an ordinary glassware round-bottom flask to a solution of PFP-DA (5 equiv.) in dry CH2Cl2 (1.5 mL) at room temperature, water (5 equiv.) was added. Forthwith the hydrolysis occurred, the resulting mixture was placed in cooling bath (acetonitrile/dry ice). To the cooled reaction mixture ( 30 8C) NXS or DBH (2.5 equiv.) and HMPA (2.0 equiv.) were added, and the whole was stirred at the temperature for next 30 min. A solution of alkene (1 equiv.) in CH2Cl2 (1.5 mL) was added dropwise, cooling bath was removed and the reaction mixture was allowed to stand at room temperature for 24 h. When the reaction was complete the appropriate amount of NMR internal standard, m-fluorotoluene (1 equiv.), was added and a sample analyzed by NMR.Under a nitrogen atmosphere, nickel bromide (4.4 mg, 0.02 mmol), 4, 4'-dimethyl-2, 2'-bipyridine (3.68 mg, 0.02 mmol), Tetrabutylammonium iodide (14.77 mg, 0.04 mmol) manganese powder (43.95 mg, 0.8 mmol), Add solvent NMP (0.5 mL) and stir well.Weigh 4-bromobiphenyl (46.62mg, 0.2mmol) in NMP (0.5mL), After dissolution, add (2-bromo-1-fluoroethyl) benzene (60.92 mg, 0.3 mmol) and mix well.The solution was transferred to a sealed tube. After sealing, the reaction was stirred in an oil bath at 80 C for 24 hours.The reaction solution was cooled to room temperature, and an equal volume of a saturated ammonium chloride solution was added to the diluted reaction solution with ether (5 mL), filtered through a diatomaceous earth funnel, rinsed with a small amount of ether, and the filtrate was collected.The filtrate was extracted three times with diethyl ether, and the organic phases were combined (add internal standard dodecane, GC-MS determined crude yield). Dry over anhydrous sodium sulfate, filter, and remove the solvent by distillation under reduced pressure.After the residue was separated by silica gel column chromatography, the product was weighed.The calculated yield was 39%.Under a nitrogen atmosphere, nickel bromide (4.4 mg, 0.02 mmol), 4, 4'-dimethyl-2, 2'-bipyridine (3.68 mg, 0.02 mmol), Tetrabutylammonium iodide (14.77 mg, 0.04 mmol) manganese powder (43.95 mg, 0.8 mmol), Add solvent NMP (0.5 mL) and stir well. Weigh 4-bromoacetophenone (39.81mg, 0.2mmol) in NMP (0.5mL), After dissolution, add (2-bromo-1-fluoroethyl) benzene (60.92 mg, 0.3 mmol) and mix well.The solution was transferred to a sealed tube. After sealing, the reaction was stirred in an oil bath at 80 C for 24 hours.Cool the reaction to room temperature, ether (5mL)Add an equal volume of saturated ammonium chloride solution to the diluted reaction solution.Filter through a diatomaceous sand core funnel, rinse with a small amount of ether, and collect the filtrate.The filtrate was extracted three times with diethyl ether, and the organic phases were combined (add internal standard dodecane, GC-MS determined crude yield). Dried over anhydrous sodium sulfate, Filtration, distillation to remove the solvent under reduced pressure, After the residue was separated by silica gel column chromatography, the product was weighed.The calculated yield was 39%.Under a nitrogen atmosphere, nickel bromide (4.4 mg, 0.02 mmol), 4, 4'-dimethyl-2, 2'-bipyridine (3.68 mg, 0.02 mmol), Tetrabutylammonium iodide (14.77 mg, 0.04 mmol) manganese powder (43.95 mg, 0.8 mmol), Add solvent NMP (0.5 mL) and stir well. Weigh 4-iodobenzaldehyde (46.40mg, 0.2mmol) in NMP (0.5mL), After dissolution, add (2-bromo-1-fluoroethyl) benzene (60.92 mg, 0.3 mmol) and mix well.The solution was transferred to a sealed tube. After sealing, the reaction was stirred in an oil bath at 80 C for 24 hours.Cool the reaction to room temperature, ether (5mL)Add an equal volume of saturated ammonium chloride solution to the diluted reaction solution.Filter through a diatomaceous sand core funnel, rinse with a small amount of ether, and collect the filtrate.The filtrate was extracted three times with diethyl ether, and the organic phases were combined (add internal standard dodecane, GC-MS determined crude yield). Dry over anhydrous sodium sulfate, filter, and remove the solvent by distillation under reduced pressure.After the residue was separated by silica gel column chromatography, the product was weighed, and the calculated yield was 46%.To a 4 mL vial, N-phenyl-N-(4-piperidyl)propanamide (25.6 mg, 0.11 mmol), K2CO3 (30 mg, 0.22 mmol), KI (9.4 mg, 0.06 mmol) were added with a magnetic stir bar. Acetonitrile (5 ml) was charged to the flask and then (2-bromo-l-fluoroethyl) benzene (37.1 mg, 0.18 mmol) was added. The reaction was allowed to stir at 115 C for 2 days. A sample aliquot was taken from the reaction, diluted with DCM in a microtube, and washed with half-saturated aq. Na2CCb. The organic layer was separated and analyzed by LCMS to confirm reaction completion. The reaction was concentrated under reduced pressure, and the crude material was dissolved in a minimal amount of DCM and dry loaded on celite. The celite/crude material was loaded onto a 10 g column which was connected to a l2 g Cl8 column and purified by reverse phase chromatography (12 g C18; 0-95% MeOH/water) to give S13 as a clear yellow oil (10 mg, 25%). 0.68; LC/MS tR = 1.42 min (Characterization Method A); m/z = 354.85 (M + H); NMR (300 MHz, CD2CI3) d = 7.46 - 7.27 (m, 8 H), 7.12 - 7.04 (m, 2 H), 5.69 - 5.44 (m, 1 H), 4.69 (tt, J = 4.0, 12.2 Hz, 1 H), 3.12 - 2.97 (m, 2 H), 2.87 (ddd, J = 9.3, 14.4, 17.2 Hz, 1 H), 2.64 - 2.43 (m, 1 H), 2.39 - 2.20 (m, 2 H), 1.93 (q, J = 7.4 Hz, 2 H), 1.86 - 1.74 (m, 2 H), 1.58 - 1.37 (m, 2 H), 1.02 (t, J = 7.5 Hz, 3 H).

Molecular Weight:203.05
XLogP3:2.9
Hydrogen Bond Acceptor Count:1
Rotatable Bond Count:2
Exact Mass:201.97934
Monoisotopic Mass:201.97934
Heavy Atom Count:10
Complexity:89.3
Undefined Atom Stereocenter Count:1
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes