Electric Literature of 446-59-3, Each compound has different characteristics, and only by selecting the characteristics of the compound suitable for a specific situation can the compound be applied on a large scale. 446-59-3, name is 2-Bromo-1-fluoro-3-methoxybenzene, This compound has unique chemical properties. The synthetic route is as follows.
Synthesis of 3-Bromo-2-fluoro-4-methoxy-benzaldehyde In a 3-neck 250 mL round bottomed flask equipped with nitrogen lines and a stir bar was placed 2-bromo-1-fluoro-3-methoxy-benzene (2.0 g, 9.75 mmol) and dichloromethane (48 mL). The solution was cooled in an ice water bath for 15 minutes and then titanium tetrachloride (5.02 mL, 45.8 mmol) and dichloromethyl methyl ether (1.32 mL, 14.6 mmol) were added and the reaction mixture was allowed to warm to room temperature and react for 2 hours. The reaction mixture was slowly added to ice water (250 mL) and extracted with dichloromethane (2*100 mL). The organic portions were combined, washed with a saturated sodium bicarbonate solution (75 mL), water (75 mL) and brine (75 mL), dried (MgSO4) and concentrated. The crude material was triturated with hexanes (15 mL) to produce 1.67 g of Int-4 as an off-white solid in 74% yield. MS (ESI+): 233.2 (M+) Int-17Synthesis of 3-Bromo-2-fluoro-4-methoxy-benzaldehyde using titanium(IV)chlorideA solution of 2-bromo-3-fluoroanisol (5.00 g, 24.3 mmol) in dichloromethane (120 mL) was cooled to 0 C. in a salt-ice bath and purged with nitrogen. The reaction was allowed to stir 15 min under nitrogen. To the reaction was added titanium(IV)chloride (23.1 g, 122 mmol), followed by a,a-dichloromethyl-methylether (4.21 g, 36.6 mmol) at 0 C. under nitrogen. The reaction was allowed to warm to room temperature and stirred for 22 h. The red solution was poured into ice water (600 mL), and extracted into dichloromethane (3×200 mL). The organic extracts were combined, washed with saturated aqueous sodium bicarbonate (2×400 mL), water (2×400 mL), and brine (400 mL), dried over sodium sulfate, filtered, and the solvent removed under vacuum to give wet product. The product was dried in a vacuum oven at 80 C. overnight to give Int-17 (5.75 g, quantitative yield).1H NMR (400 MHz CDCl3) delta 10.22 (s, 1H), 7.86 (dd, J=8.8 Hz, 7.6 Hz, 1H), 6.82 (d, J=8.4 Hz, 1H), 4.01 (s, 3H). Synthesis of 3-bromo-2-fluoro-4-methoxy-benzaldehyde (I-30). In a 3-necked 250 mL round-bottomed flask equipped with nitrogen lines and a stir bar was placed 2-bromo-1-fluoro-3-methoxy-benzene (I-29, 2.0 g, 9.75 mmol) and dichloromethane (48 mL). The solution was cooled in an ice water bath for 15 minutes and then titanium tetrachloride (5.02 mL, 45.8 mmol) and dichloromethyl methyl ether (1.32 mL, 14.6 mmol) were added and the reaction mixture was allowed to warm to room temperature and react for 2 hours. The reaction mixture was slowly added to ice water (250 mL) and extracted with dichloromethane (2×100 mL). The organic portions were combined, washed with a saturated sodium bicarbonate solution (75 mL), water (75 mL) and brine (75 mL), dried (MgSO4) and concentrated. The crude material was triturated with hexanes (15 mL) to produce 1.67 g of 3-bromo-2-fluoro-4-methoxy-benzaldehyde (I-30) as an off-white solid in 74% yield. MS (ESI+): 233.2 (M+).
The chemical industry reduces the impact on the environment during synthesis 2-Bromo-1-fluoro-3-methoxybenzene. I believe this compound will play a more active role in future production and life.
Reference:
Patent; DECODE GENETICS EHF; US2009/136473; (2009); A1;,
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