2-Bromo-4-chloroanisole

Clear colorless to pale yellow liquid

2-Bromo-4-chloro-1-methoxybenzene (47). A solution of sodium hydroxide (836 mg, 20.9 mmol) in water (8.0 mL) was added to a solution of 2-bromo-4-chlorophenol (45) (2.1 g, 9.92 mmol) and tetrabutylammonium bromide (336.4 mg, 1.03 mmol) in dichloromethane. Dimethyl sulfate (1.5 mL, 15.69 mmol) was added. The resulting mixture was stirred at room temperature for 22 h and then 1 N aq HCl (about 2 mL) was added to quench the reaction. The organic phase was separated and the aqueous phase was extracted with dichloromethane (2.x.15 mL). The combined organic phase was washed with brine, dried over sodium sulfate and concentrated to afford an oil. The crude product was purified by column chromatography on silica gel (10 g) using EtOAc-hexanes (5percent) to afford the product 47 as a colorless oil (2.17 g) in 99percent yield. See, Dischino, D. D.; Gribkoff, V. K.; Hewawasam, P.; Luke, G. M.; Rinehart, J. K.; Spears, T. L.; Starrett Jr, J. E. Synthesis of 3H and 14 C Labeled (S)-3-(5-Chloro-2-methoxyphenyl)-1, 3-dihydro-3-fluoro-6-(trifluoromethyl)-2H-indol-2-one, Maxipost.(TM).. An Agent for Post-Stroke Neuroprotection. J. Label. Compd. Radiopharm. 2003, 46, 139-149, the disclosure of which is incorporated herein by reference. General procedure: To a stirred solution of 7aa (19.11 g, 0.10 mol) or 7ab (20.75 g, 0.10 mol) in acetone (150 mL) was added KEXAMPLE 109 EXAMPLE 109 [001171 2-Bl'Omo-4-chloro-1-methoxybenzene (54) (Hamashima, N a/., J. Am. Chern. Soc.127:10 J 64-10165 (2005;;: To a solution of l6b (151 mg, 0.416 mmol) in CH2Cl2 (5 mL) wasadded bruminc (100 mg, 0.626 mmol) at 0 °C, and the reaction mixture was stirred at 23 ocfor 1 h. The reaction was then quenched witl1 Na2S201 (30percent aqueous solution, 2 rnL) at 0oc. The aqueous phase was extracted with ethyl acetate. the combined organic layer wasdried over MgS04, filtered. and tl1e solvent was evaporated in vacuo. The residue waspurified by flash colunrn chromatography (0-710percent ethyl acetate in hexane:>) to give theproduct as a colorless liquid (8 l .6 rng. 89percent yield). 1H NMR (600 Mfiz, CDCh) o 7.53 (d . .J=2.4Hz, IH), 7.24(dd, J=8.8, 2.4Hz, IHJ, 6.81 (d, J=8.8Hz, IH), 3.87(s, 3H). t.lCNMR (151 MHz, CDCb) o 154.87 (s), 132.93 (s), 128.41 (s), 126.07 (:>), 112.64 (s), 112.23(s). 56.58 (s).To a reaction tube charged with NBS (1.5 equiv, 0.3 mmol), catalyst (10 molpercent, 0.02 mmol) and CHEXAMPLE 109 EXAMPLE 109 EXAMPLE 109 EXAMPLE 109 Into a round-bottom flask equipped with a stir bar and nitrogen on demand were placed 2-Bromo-4-chloro-1-methoxybenzene (47). A solution of sodium hydroxide (836 mg, 20.9 mmol) in water (8.0 mL) was added to a solution of 2-bromo-4-chlorophenol (45) (2.1 g, 9.92 mmol) and tetrabutylammonium bromide (336.4 mg, 1.03 mmol) in dichloromethane. Dimethyl sulfate (1.5 mL, 15.69 mmol) was added. The resulting mixture was stirred at room temperature for 22 h and then 1 N aq HCl (about 2 mL) was added to quench the reaction. The organic phase was separated and the aqueous phase was extracted with dichloromethane (2×15 mL). The combined organic phase was washed with brine, dried over sodium sulfate and concentrated to afford an oil. The crude product was purified by column chromatography on silica gel (10 g) using EtOAc-hexanes (5%) to afford the product 47 as a colorless oil (2.17 g) in 99% yield. See, Dischino, D. D.; Gribkoff, V. K.; Hewawasam, P.; Luke, G. M.; Rinehart, J. K.; Spears, T. L.; Starrett Jr, J. E. Synthesis of 3H and 14 C Labeled (S)-3-(5-Chloro-2-methoxyphenyl)-1, 3-dihydro-3-fluoro-6-(trifluoromethyl)-2H-indol-2-one, Maxipost. An Agent for Post-Stroke Neuroprotection. J. Label. Compd. Radiopharm. 2003, 46, 139-149, the disclosure of which is incorporated herein by reference. 1H NMR (300 MHz, CDCl3) delta 7.51 (d, J=2.4 Hz, 1H), 7.22 (dd, J=2.4 Hz, J=8.7 Hz, 1H), 6.80 (d, J=8.7 Hz, 1H), 3.86 (s, 3H).

Molecular Weight:221.48
XLogP3:3.4
Hydrogen Bond Acceptor Count:1
Rotatable Bond Count:1
Exact Mass:219.92906
Monoisotopic Mass:219.92906
Topological Polar Surface Area:9.2
Heavy Atom Count:10
Complexity:110
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes