4-Fluoro-3-nitrobenzyl bromide

Compound 1a-2: 2-Bromoznethyl-4-fluoro-3-nitrobenzene; Phosphorus tribromide (1.13 mL) was added to a solution of 4-fluoro-3-nitrobenzyl alcohol (2.1 g, 11.23 mmol) in diethyl ether (40 mL), and the mixture was stirred at room temperature for 1 hour. Water was then added to the reaction mixture, and extraction was performed with ethyl acetate. The organic extract was washed with saturated sodium hydrogen carbonate solution and saturated saline. After drying over magnesium sulfate and concentrating under reduced pressure, the resultant residue was purified by column chromatography to yield the title compound (2.50 mg, 95percent) as a pale yellow solid. Phosphorus tribromide (1.13 mL) was added to a solution of 4-fluoro-3-nitrobenzyl alcohol (2.1 g, 11.23 mmol) in diethyl ether(40 mL), and the mixture was stirred at room temperature for 1 hour. Water wasthen added to the reaction mixture, and extraction was performed with ethylacetate. The organic extract was washed with saturated sodium hydrogencarbonate solution and saturated saline. After drying over magnesium sulfateand concentrating under reduced pressure, the resultant residue was purified bycolumn chromatography to yield the title compound (2.50 mg, 95percent) as a paleyellow solid.A solution of 4-fluoro-3-nitrobenzylalcohol (3.04 g, 17.8 mmol) in ether (20 ml) was added dropwise to a solution of phosphorus tribromide (1.92 g, 7.11 mmol) in ether (80 ml) at 0 °C, and the mixture was stirred for 2 h at ambient temperature. The reaction mixture was washed with saturated aqueous sodium bicarbonate and brine, dried with sodium sulfate, and evaporated to afford 16 (pale yellow solids, 3.41 g, 14.6 mmol, 82percent). Mp 55.5-56.0 °C; 4-(Bromomethyl)-l-fluoro-2 -nitrobenzene (3):4-Fluoro-3-nitrobenzyl alcohol (50g, 290 mmol, subject compound 2) is dissolved in500 ml of dichloromethane, and is cooled to 0°C with an ice-salt bath. To this solution is added drop-wise phosphorus tribromide (27.5 mL, 290 mmol) at 0°C, and the reaction is continued at room temperature for 2 h. After the reaction is completed as indicated by TLC, the reaction is quenched with ice water, extracted with dichloromethane, washed with saturated saline, and dried over anhydrous sodium sulfate. The solvent is removed to give a yellowish solid, which is recrystallized (n-hexane: ethyl acetate = 1 : 1) to give a white solid (subject compound 3, 54 g, 79.9percent).To a stirred solution of 4-fluoro-3-nitrobenzyl alcohol (14) (4.50 g, 26.31 mmol) in anhydrous Et2O (52 mL) at 0 °C wasadded dropwise PBr3 and stirred for 15 min under nitrogen atmosphere. The reaction mixturewas quenched with water (30 mL) and extracted with Et2O (2 × 80 mL). The combined organicphases was washed with saturated NaHCO3 solution (50 mL) and brine (50 mL), dried over anhydrous Na2SO4, and then evaporated to dryness under reduce pressure. The residue waspurified by MPLC on silica gel using hexane/EtOAc (8:1) as eluent to give the titled compound as a pale yellow solid. Yield 54percent.General procedure: b. The sodium hydride solid (1.5 eq) was added into a mixture of intermediate 2 (1.0 eq) and corresponding benzyl bromide (1.2 eq) in parallel reaction tube, DMSO as solvent. N2 was used to remove water vapor and oxygen. The reaction mixture was stirred at room temperature overnight. The degree of reaction was detected by TLC. After the reaction was completed, adding water to quench to precipitate solid. Filtered, washed and dried, and intermediate 3b was gained. The yield was 60%.

scaffold molecule for combinatorial synthesis

Molecular Weight:234.02
XLogP3:2.4
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:1
Exact Mass:232.94877
Monoisotopic Mass:232.94877
Topological Polar Surface Area:45.8
Heavy Atom Count:12
Complexity:173
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes