4-bromo-1-iodo-2-methoxybenzene

A stirred solution of NaN0A stirred solution of NaN0A stirred solution of NaNO4-Bromo-2-methoxy-aniline (20 g, 99 mmol) was dissolved in water (695 mL) and concentrated sulphuric acid (113 ML). The solution was cooled to 0 °C and sodium nitrite (7.5 g, 109 mmol) dissolved in water (32 mL) was added and stirred for 1 hour at 5-10 °C. POTASSIUM iodide (21.4g, 129 mmol) dissolved in water (100 mL) was added slowly whilst the mixture was virgorously stirred. After addition, the mixture was allowed to warm to room temperature. Ethyl acetate was added and the phases were separated. The aqueous phase was extracted with ethyl acetetate (3 X). The combined organic phases were then washed with 1M NAOH, 1M Na2S203, 1M HCl, - 1M saturated NAHCO3 and brine. The separated organic phase was dried (MGS04), filtered and concentrated in vacuo. The product was purified by flash chromatography using silica gel and eluting with HEPTANE/ETHYL acetate 1: 1. The product was identified from relevant fractions which were combined and concentrated IN VACUO. Yield: 24.12g, 78percentTo a mixed solution of 2.0 g (9.0 mmol) of 4-bromo-2-methoxy aniline (Tokyo Chemical Industry Co., Ltd.) in acetic acid (15 ml)-concentrated hydrochloric acid (1 ml) was added 0.75 g (11 mmol) of sodium nitrite under ice cooling while stirring so that the internal temperature did not exceed 10°C, and the mixture was stirred at room temperature for 30 minutes. Then, the reaction mixture was added dropwise to a solution of 1.0 g (30 mmol) of potassium iodide in a 48percent by weight aqueous hydrobromic acid solution (30 ml) at room temperature while stirring, and the mixture was stirred at the same temperature for one hour. After completion of the reaction, to a mixture of an aqueous sodium carbonate solution and methylene chloride was added the reaction mixture portionwise, the basicity of the aqueous layer was confirmed, and an extraction with methylene chloride from the mixed solution was subsequently conducted. The organic layer was washed sequentially with a 10percent by weight aqueous sodium hydrogen sulfite solution, a saturated aqueous sodium hydrogencarbonate solution and saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The resulting residue was subjected to silica gel column chromatography (elution solvent; hexane:ethyl acetate = 100:0 to 91:9 (V/V)), and the fractions containing the desired compound were concentrated under reduced pressure to obtain 2.2 g (7.2 mmol, yield 73percent) of the title compound as an orange solid. Mass spectrum (EI, m/z): 312 [M](Reference Example 3) To a solution of 4-bromo-2-methoxyphenyl)amine (11 Og, 0.54mol) in CH4-Bromo-2-methoxy-phenylamine (2.02 g, 10 mmol) was added to a solution of p-toluensulphonic acid monohydrate (3.80 g, 20 mmol) in acetonitrile (30 mL). The mixture was cooled in an ice bath and treated with an solution of sodium nitrite (0.69 g, 10 mmol) and potassium iodide (4, 15 g, 25 mmol) in water (7 mL) over 15 min maintaining the internal temperature below 10 °C. After stirring at that temperature for 15 min and then for 0.5 h at room temperature, the reaction mixture was diluted with water and extracted with EtOAc (5 x 50 mL). The combined organic extracts were washed with 2M sodium thiosulfate (10 mL), brine (4 x 20 mL), water (20 mL), anhydrified over sodium sulphate, and evaporated to dryness affording a black oil that was purified by flash chromatography (petroleum ether/ferf-butylmethyl ether 5/1) to yield the title compound (1.63 g, 52.2percent).To a solution of 5-bromo-2-iodo-phenol (1.00 g, 3.35 mmol) in acetone (10.0 mL) was added iodomethane (951 mg, 6.70 mmol) and anhydrous potassium carbonate (926 mg, 6.70 mmol) at it. The reaction mixture was stirred at it for 12 hrs. On completion, the reaction mixture was filtered. The filtrate was concentrated in vacuo. The residue was purified by silica gel chromatography (petroleum ether) to give the title compound (1.00 g, 96percent yield). MR (400MHz, CDC13) δ = 7.61 (d, J =8.4 Hz, 1H), 6.95 (d, J =1.8 Hz, 1H), 6.87 (dd, J =8.4 Hz, 1.8 Hz, 1H), 3.89 (s, 3H).

Molecular Weight:312.93
XLogP3:3.2
Hydrogen Bond Acceptor Count:1
Rotatable Bond Count:1
Exact Mass:311.86467
Monoisotopic Mass:311.86467
Topological Polar Surface Area:9.2
Heavy Atom Count:10
Complexity:110
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes