4-Bromophenol (2). A single-necked (24/40 joint) 250 mL round-bottomed flask is equipped with a Teflon-coated magnetic stir bar (3.0 x 1.5 cm, footballshaped). The apparatus is flame-dried under reduced pressure and cooled to 23 °C under an atmosphere of nitrogen. The flask is then equipped with a rubber septum and then placed under positive pressure of nitrogen using a nitrogen inlet. To the flask is then added (4-bromophenol)(tertbutyl) dimethylsilane (1) (4.5 g, 3.8 mL, 16 mmol, 1.0 equiv) (Note 2) via syringe. Then, dry THF (30 mL) (Note 3) is added at 23 °C to the flask via syringe and stirring is started (300 rpm). After one min of stirring, tetrabutylammonium fluoride solution (19 mL, 1.0 M in THF, 19 mmol, 1.2 equiv) (Note 4) is added via syringe dropwise over five min (Figure 1A). The reaction mixture is then allowed to stir (300 rpm) at 23 °C for 30 min (Note 5). Then, the rubber septum is removed, and calcium carbonate (8.2 g, 82 mmol, 5.3 equiv) (Note 6) is added in one portion followed by Dowex 50WX8, 200–400 mesh, ion exchange resin (24 g) (Note 7) in two equal portions using a funnel to assist with the addition. To the reaction mixture is then added methanol (60 mL) (Figure 1B) (Note 8), the rubber septum is replaced, including the nitrogen inlet, and the suspension is stirred for 1 h at 23 °C (900 rpm).
The resulting mixture is then filtered through a wetted celite pad (28 g, wetted with methanol (100 mL)) (Note 9) (7 x 4 cm) in a 150 mL medium porosity fritted Büchner funnel into a 1 L round-bottomed flask (24/40 joint) (Figure 2) using methanol (300 mL) as the eluent (Note 10).
The filtrate is then concentrated by rotary evaporation (30 °C, 150 mmHg to 15 mmHg) under reduced pressure to yield a biphasic mixture of a colorless liquid and a yellow liquid. The 1 L round-bottomed flask is then charged with silica gel (10.0 g) (Note 11). The crude material and silica gel are suspended in methylene chloride (60 mL) (Note 12) and concentrated under reduced pressure (30 °C, 375 mmHg to 22 mmHg) until a fine powder results. The product-adsorbed silica is then added to a column (7 cm OD x 20 cm tall) which is prepared using silica gel (165 g) that is wetted with pentane (500 mL) (Notes 13 and 14) (Figure 3A, 3B). The column is then eluted with 19:1 pentane:diethyl ether (2 L) (Note 15), followed by 9:1 pentane:diethyl ether (1 L), followed by 4:1 pentane:diethyl ether (1 L).
The product is collected in 55 mL culture tubes, and the desired product elutes in fractions 35–66 (Note 16). These fractions are pooled and concentrated under reduced pressure (30 °C, 300 mmHg to 22 mmHg). The resulting yellow oil is then transferred to an 8-dram vial using diethyl ether and concentrated under reduced pressure (30 °C, 300 mmHg to 22 mmHg).Then, the resulting oil is dried under high vacuum at 23 °C for 18 h (Note 17) to yield a crystalline white solid (2.44 g, 88% yield, 98% purity) (Notes 18, 19, 20, and 21).
参考资料
一、Org. Lett. 2007, 9, 4, 723–726；https://doi.org/10.1021/ol063113h
二、Org. Synth. 2022, 99, 53-67；DOI: 10.15227/57 orgsyn.099.0053
