3-Bromo-2-fluorobenzenamine

Under argon, 1.0 g (4.54 mmol) of 3-bromo-2-fluoronitrobenzene was initially charged in 5 ml of dioxane, and 4.3 g (22.72 mmol) of tin(II) chloride and a few drops of 1 N hydrochloric acid were added. After 2 h of stirring, the reaction mixture was concentrated on a rotary evaporator and the residue was taken up in ethyl acetate. The organic phase was washed with 1 N aqueous sodium hydroxide solution, water and saturated sodium chloride solution and then dried over magnesium sulfate and concentrated. This gave 826 mg (95percent of theory) of the title compound.LC-MS (method 15): RTo a mixture of l-bromo-2-fluoro-3 -nitrobenzene (13.75 g, 62.76 mmol), HO Ac (26.36 g, 439 mmol), EtOH (150 mL) and HTo a mixture of 1-bromo-2-fluoro-3-nitrobenzene (13.75 g, 62.76 mmol), HOAc (26.36 g, 439 mmol), EtOH (150 mL) and H20 (60 mL) at room temperature, iron powder (9.14 g, 163 mmol) was added portion-wise. The resultingmixture was stirred at room temperature for 16 h and then was neutralized with NaOH(5 N) solution. Then the mixture was extracted with ethyl acetate. The organic layerwas washed with brine, dried over Na2SO4 and concentrated in vacuo. The residue waspurified by flash column chromatography on silica gel (petroleum ether / ethyl acetate =10 : 1) to afford the desired product (7.77 g, 65percent yield) as a brown oilTo a mixture of 1-bromo-2-fluoro-3-nitrobenzene (13.75 g, 62.76 mmol), acetic acid (26.36 g, 439 mmol), ethanol (150 mL) and H3-Bromo-2-fluorobenzenamine Example 17A3-Bromo-2-fluoroaniline; 2.0 g (9.09 mmol) of 3-bromo-2-fluoronitrobenzene were dissolved in 10 ml of dioxane, and 8.62 g (45.45 mmol) of tin(II) chloride were added at RT. After addition of a few drops of 1 N hydrochloric acid, the mixture was heated at 70° C. for 2 h. After cooling, the reaction mixture was concentrated under reduced pressure and the residue was taken up in ethyl acetate. The solution was washed successively twice with 1 N aqueous sodium hydroxide solution, water and saturated sodium chloride solution, dried over magnesium sulphate and concentrated under reduced pressure. The crude product was purified by chromatography on silica gel (mobile phase cyclohexane/ethyl acetate 10:1). This gave 997 mg (57.7percent of theory) of the target compound.LC-MS (Method 6): R31.1) 3-Bromo-2-fluoro-phenylamine (Intermediate 96):1-Bromo-2-fluoro-3-nitro-benzene (3 g, 13.64 mmol), iron (2.28g, 40.91 mmol), water (34.39 ml, 1909 mmol) and acetic acid (11.7 ml, 204.55 mmol) were added to ethanol (60 ml) and heated to reflux for 2 h. The reaction mixture was then filtered through celite and evaporated. Water was added and the solution was made basic by the addition of 2 N NaOH, followed by extraction with DCM. The organic layers were washed with water and brine, dried with NaStep 1 : A solution of 3-bromo-2-fluoro-nitrobenzene (8.4 g, 38.2 mmol) in (2:2: 1) EtOH/AcOH/H3-Bromo-2-fluorobenzenamine To a mixture of 1-bromo-2-fluoro-3-nitrobenzene (13.75 g, 62.76 mmol), HOAc (26.36 g, 439 mmol), EtOH (150 mL) and HA solution of tert-butoxy-N-(3-bromo-2-fluorophenyl)carboxamide (17.7 g, 59.5 mmol) in 5 N HCl/1, 4-dioxane (500 mL) was stirred at room temperature for 18 hours. To 3-bromo-2-fluorobenzoicacid (10.0 g, 45.7 mmol) in 100 mL of toluene, were added by EtStep 1: 3-bromo-2-fluoroaniiTo a stirred solution of 3-bromo-2-fluoro benzoic acid (10 g, 0.04566 mol) in Ν, Ν-dimethyl formamide (80 mL), were added dropwise triethylamine (19 ml_, 0.13669 mol) and diphenylphosphoryl azide (14.8 mL, 0.05378 mol) at 0°Csequentially. The reaction mixture was stirred for 2 h at 0°C. Water (27 mL) was added and the reaction mixture was heated at 80 °C for 2 h. The reaction mixture was cooled to room temperature, diluted with water (200 mL) and extracted with diethyl ether (3x150 mL). The combined organic layers were washed with cold water (2x200 mL), dried over anhydrous sodium sulfate and evaporated under reduced pressure.The residue obtained was treated with hexane (100 mL), filtered, and the filter cake was washed with hexane (2x100 mL). The filtrate was evaporated under reduced pressure to afford the title compound (4.3 g, 50percent) as a brown liquid. H NMR (400 MHz, DMSO-d

Molecular Weight:190.01
XLogP3:2
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:2
Exact Mass:188.95894
Monoisotopic Mass:188.95894
Topological Polar Surface Area:26
Heavy Atom Count:9
Complexity:99.1
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes