4-Bromo-2-iodoaniline

Grey to purple powder

General procedure: General procedure for the iodination of aryl amines under solvent-free conditions.DBDABCODCI (0.5 mmol) and aryl amine (1 mmol) were triturated together in a porcelainmortar at room temperature. After completing reaction which monitored by TLC, the ethylacetate added to mixture and filtered, the organic layer washed with 5percent aqueous sodiumthiosulfate, and dried over MgSO4. The solvent was removed in vacuum and the crude mixturewas purified by column chromatography using ethyl acetate and hexane mixture and analyzedby m.p. and 1H NMR spectroscopy.To a solution of 4-bromo-aniline (500 g, 2.90 mol, 2.0 equiv, Saibain Chem) in cyclohexane (2.5 L) was added iodine (368 g, 1.45 mol, 1.0 equiv, Qualigens) and the mixture was heated at 50° C. To a solution of 4-bromo-aniline (500 g, 2.90 mol, 2.0 equiv, Saibain Chem) in cyclohexane (2.5 L) was added iodine (368 g, 1.45 mol, 1.0 equiv, Qualigens) and the mixture was heated at 50 °C. After 30 min, the reaction mixture became homogenous. 30percent aqueous hydrogen peroxide solution (250 mL, Spectrochem) was added to the reaction mixture. The reaction was heated for 4 h at 50 °C. The reaction was cooled to room temperature, diluted with ethyl acetate (5.0 L) and washed with aqueous sodium-sulphite (2.5 Kg in 4.0 L) solution. The organic layer was washed with water (3.0 L) and brine (3.0 L) dried over magnesium sulfate, filtered and concentrated under reduced pressure to obtain the crude material which was purified by column chromatography (silica gel; mesh size 60-120, elution 0-20percent ethyl acetate and hexanes) to get 4-bromo-2-iodoaniline (650 g, 75.0 percent), as off white solid. TLC solvent system: 100 percent hexanes. Product's RA vigorously stirred suspension of 2-iodoaniline (10. 0 g, 45.7 MMOL), potassium bromide (6.52 g, 54.8 MMOL), and ammonium molybdat tetrahydrate (0.57 g, 0.46 MMOL) in acetic acid (54 mL) was cooled to 0°C, treated with sodium perborate (7.74 g, 50.3 MMOL), and stirred for two hours as the reaction warmed to room temperature. After adding water and stirring one additional hour, the reaction mixture was poured into ice-water and filtered. The filtered solid was washed with water, dissolved in ethyl acetate (250 mL), and washed with a saturated, aqueous, potassium carbonate solution (2 x 75 mL). The organic phase was dried over anhydrous sodium sulfate, filtered, and concentrated in vacuo to afford the intermediate, 4 bromo-2- iodoaniline, as a red solid (12.56 g, 92percent). [0196] 5-Bromo-4'-fluoro-1, 1'-biphenyl-2-ylamine was prepared from the above intermediate, 4-bromo-2-iodoaniline (12.6 g, 42.2 MMOL), 4-FLUOROPHENYLBORONIC acid (5.9 g, 42 MMOL), [1, 1'-bis (diphenylphosphino) ferrocene] DICHLOROPALLADIUM (II) COMPLEX with DICHLOROMETHANE (0.69 g, 0.84 MMOL), and a 5 N aqueous sodium hydroxide solution (85 mL, 425 MMOL) according to the procedure and in the same manner as described in Example 32, Method A, Step a. [0197] The title compound was prepared from the above 5-bromo-4'-fluoro-1, 1'- biphenyl-2-ylamine (10.1 g, 37.8 MMOL), propionic anhydride (5.33 mL, 41.6 MMOL), 4- (N, N-dimethylamino) pyridine (0.46 g, 3.8 MMOL), and pyridine (12.3 mL, 151 MMOL), according to the same procedure, to yield N- (5-BROMO-4APOS;-FLUORO-1, 1APOS;-BIPHENYL-2- YL) propanamide as a solid (7.74 g, 64percent from 4-bromo-2-iodoaniline), m. p. 133°C ; MS [(-ESI), M/Z] : 320 [M-H]- ; 'H NMR (500 MHz, DMSO-d6) S : 9.21 (s, 1 H), 7.52 (dd, J = 2.4, 8.5 Hz, 1 H), 7.47 (d, J = 2.2 Hz, 1H), 7.43-7. 38 (m, 3H), 7.28-7. 23 (m, 2H), 2.13 (q, J = 7.5 Hz, 2H), 0.95 (t, J = 7. 5 HZ, 3H); Anal. CALCD for C15H13BRFNO : C, 55.92 ; H, 4.07 ; N, 4.35. Found: C, 55.79 ; H, 4.08 ; N, 4.31A solution of 2-iodoaniline (271.4 mg, 1.24 mmol, 1.0 equiv) in DCM (2.0 mL) at 0 °C wasadded with NBS (243.5 mg, 1.38 mmol, 1.1 equiv) and was allowed to stir at 0 °C while slowlywarming to room temperature over 3 h. The reaction mixture was then added with water and theseparated aqueous mixture was extracted with EtOAc (3x times). The combined organic phaseswere washed with sat. aq. NaCl, dried over anh. Na2SO4 and concentrated under reducedpressure. The crude material was purified by SiO2 column chromatography eluting with 10percentEtOAc-hexane to yield 319.0 mg of 4-bromo-2-iodoaniline (86percent) as a pink crystal).

Molecular Weight:297.92
XLogP3:2.6
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:1
Exact Mass:296.86501
Monoisotopic Mass:296.86501
Topological Polar Surface Area:26
Heavy Atom Count:9
Complexity:99.1
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes