(3-bromo-2-fluoro-4-methoxyphenyl)methanol

反応条件: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Into a 100 mL round bottom flask was added (3-bromo-2-fluoro-4-methoxy-phenyl)-methanol (I-31, 1.04 g, 4.0 mmol), 3-chlorophenylboronic acid (0.76 g, 4.8 mmol), Pd(PPh3)4 (0.45 g, 0.41 mmol), Na2CO3 (6 mL, 2M aq), toluene, (32 mL), and EtOH (11 mL). The reaction was degassed with N2, then stirred at 80° C. for 24 hours. Water was added and the product was extracted with ethyl acetate. The combined organics were concentrated and filtered through a SiO2 plug eluting with 50% ethyl acetate/hexanes. The solid was triturated with ether and filtered. The filtrate was concentrated and triturated with ether and filtered. The filter cakes were combined and purified by flash column chromatography eluting with 20% acetone/hexanes to give (3′-chloro-2-fluoro-6-methoxy-biphenyl-3-yl)-methanol (I-32, 0.79 g, 67%) as a white solid. The reaction was degassed with N2 Water was added the product was extracted with ethyl acetate The combined organics were concentrated filtered through a SiO2 plug eluting with 50% ethyl acetate/hexanes The solid was triturated with ether filtered The filtrate was concentrated triturated with ether filtered purified by flash column chromatography eluting with 20% acetone/hexanes

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: In a 100 mL round bottomed flask equipped with a stir bar was placed 3-bromo-2-fluoro-4-methoxy-benzaldehyde (I-30, 1.67 g, 7.17 mmol), methanol (12 mL), dichloromethane (12 mL) and sodium borohydride. The reaction mixture was allowed to stir at room temperature for 17 hours, quenched with water (10 mL) and 1M HCl (5 mL) and extracted with dichloromethane (2×30 mL). The organic portions were combined, washed with brine (30 mL), dried (MgSO4) and concentrated. The crude material was triturated with hexanes (15 mL) to produce 955 mg (57%) of (3-bromo-2-fluoro-4-methoxy-phenyl)-methanol (I-31) as a white solid. In a 100 mL round bottomed flask equipped with a stir bar quenched with water (10 mL) and 1M HCl (5 mL) extracted with dichloromethane (2×30 mL) washed with brine (30 mL) dried (MgSO4) concentrated The crude material was triturated with hexanes (15 mL)