| 38% |
With boron tribromide; In dichloromethane; at -60 - 20℃; for 17.0h; |
To a solution of Example 2d (43.1 g, 0.29 mol) in DCM (800 mL) at -60 C was added BBr3 (215 mL, 1M in DCM) dropwise. The reaction mixture was allowed to stir at room temperature for 17 h. The reaction mixture was quenched slowly with MeOH (200 mL), and basified with NaHC03 to pH~8. The organic layer was separated, dried over Na2S04, filtrated and concentrated under reduced pressure. The residue was purified by silica gel chromatography, eluting with 10% of EtOAc in Petroleum Ether, to give the desired product (Example 2e, 14.8 g, yield 38%) as white solid. 1H NMR (400 MHz, DMSO) delta 8.76 (s, 1H), 6.59 (d, J= 8.5 Hz, 1H), 6.51 (d, J= 2.8 Hz, 1H), 6.46 (dd, J = 8.5, 2.9 Hz, 1H), 3.60 (t, J= 7.6 Hz, 2H), 2.96 (t, J= 7.6 Hz, 2H). |
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2-Bromo-4-methoxyphenol (4.0 g, 19.7 mmol, 1.0 eq.), 1,2-dibromoethane (2.55 ml, 29.55 mmol, 1.5 eq.), and NaOH (946 mg, 23.6 mmol, 1.2 eq.) were mixed in water (20 ml) and tetrabutylammonium bromide (1.27 g, 3.94 mmol, 0.2 eq.) was added to it and the mixture was refluxed overnight. The reaction mixture was diluted with EtOAc (100 ml), washed with water (10 ml X 4) and brine (20 ml X 4), dried over sodium sulfate, and concentrated under reduced pressure. The crude compound was purified by column chromatography (silica gel 100-200 mesh, eluted with 2.5% EtOAc-hexane) to afford 2-bromo- 1 -(2-bromoethoxy)-4-methoxybenzene. 2-Bromo- 1 -(2-bromoethoxy)-4- methoxybenzene (2.6 g, 8.39 mmol, 1.0 eq.) in THF (10 ml) was cooled to -100 0C in argon atmosphere. n-BuLi (6.3 ml, 10.07 mmol, 1.2 eq., 1.6 M in pentane) was slowly added to the reaction mixture and stirred for 2 h, maintaining the same temperature. The reaction was quenched with saturated NH4CI (20 ml) and extracted with EtOAc (100 ml). The organic layer was washed with water (10 ml X 3) and brine and dried over sodium sulfate. The crude compound was purified by column chromatography (silica gel 100-200 mesh, eluted with 1-3 % EtOAc-hexane) to afford 5-methoxy-2,3-dihydrobenzofuran. 5- Methoxy-2,3-dihydrobenzofuran (1.34 g, 8.92 mmol, 1.0 eq.) was dissolved in DCM (25 ml) and cooled to -78 0C. Tribromoborane (2.1 ml, 22.3 mmol, 2.5 eq.) was slowly added over 10-15 minutes, the temperature was raised to ambient temperature and stirred for 2 h. The reaction was quenched with NaHCO3 and extracted with DCM (30 ml X 3), washed with water (20 ml X 3) and brine and dried over sodium sulfate. The organic layer was concentrated under reduced pressure and the residue was purified by column chromatography (silica gel 100-200 mesh, eluted with 20% EtOAc-hexane) to afford 2,3- dihydrobenzofuran-5-ol. |
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