* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.
Stage #1: With n-butyllithium In tetrahydrofuran; hexane at -78℃; for 0.75 h; Stage #2: With Trimethyl borate In tetrahydrofuran; hexane at -78℃; for 1.25 h; Stage #3: With hydrogenchloride; water In tetrahydrofuran; hexane at 20℃;
Step 1b: 4-(Tert-butyldimethylsilyloxy)phenylboronic acid (Compound 0102) To a solution of compound 0101 (1.548 g, 5.389 mmol) in dry THF (20 ml) was added dropwise a 2.5 M n-BuLi in hexane solution (2.5 ml, 6.326 mmol,) at -78° C. for 15 min under N2. After the mixture was stirred at -78° C. for 0.5 h, trimethyl borate (730 mg, 7.029 mmol) was added dropwise for 15 min to the mixture. The mixture was stirred at -78° C. for additional 1 h and warmed to room temperature. The reaction mixture was quenched with aqueous hydrochloric acid solution (to pH 5-7). The solvent was removed and the residue was extracted with DCM. The organic layer was washed with brine, dried over anhydrous Na2SO4, concentrated to give a residue which was washed by petroleum (2 ml) to afford the product 0102 as a white solid (1.102 g, 81percent): LCMS: 253 [M+1]+.
70%
Stage #1: With n-butyllithium In tetrahydrofuran; hexane at -78℃; for 1 h; Stage #2: With Triisopropyl borate In tetrahydrofuran; hexane at -78 - 20℃;
Method A. To a solution of (4-BROMO-PHENOXY)-TERT-BUTYL-DIMETHYLSILANE (20 mL, 23.48 g, 0. 082 moles) in tetrahydrofuran (200 mL) at-78 °C was slowly added n-butyl lithium (39.2 ML of 2.5 M solution in hexane, 0.098 moles) under N2 with stirring over a few minutes. The solution was stirred for 1 hour and triisopropyl borate (66.2 ML, 54.0 g, 0.29 moles) was added by syringe AT-78 °C. The solution was stirred for 1 hr at - 78 °C and then allowed to warm to room temperature overnight. The reaction was cooled to 0 °C and water (20 ML) and 2 N HC1 (20 mL) were added into the reaction mixture. Then the whole mixture was stirred with OF 2 N HC1 (360 ML) for 10 minutes. The mixture was extracted with ethyl acetate (3 x 250 mL). The combined organic layers were concentrated to a volume of about 50 mL. Crystallization was induced with cold hexane, and the solid product was collected by filtration and dried under vacuum to yield 14.5 g (70 percent) of the title compound as a white solid : 1H NMR (DMSO-D6) : 8 0.19 (6H, s), 0.94 (9H, s), 6.80 (2H, d, J= 8. 4 Hz), 7.69 (2H, d, J= 8. 36 Hz), 7. 87 (2H, s).
Reference：
[1] Journal of the American Chemical Society, 1997, vol. 119, # 25, p. 5818 - 5827
[2] New Journal of Chemistry, 2013, vol. 37, # 4, p. 961 - 964
[3] Journal of the American Chemical Society, 2009, vol. 131, # 47, p. 17443 - 17451
[4] Patent: US2009/76006, 2009, A1, . Location in patent: Page/Page column 29; 35
[5] Bioorganic and Medicinal Chemistry, 2004, vol. 12, # 10, p. 2553 - 2570
[6] Patent: WO2004/99122, 2004, A2, . Location in patent: Page 14; 19
[7] Synthesis, 2003, # 4, p. 513 - 522
[8] Bioorganic and Medicinal Chemistry Letters, 2004, vol. 14, # 3, p. 689 - 693
2
[ 71597-85-8 ]
[ 18162-48-6 ]
[ 159191-56-7 ]
Yield
Reaction Conditions
Operation in experiment
90%
With 1H-imidazole In N,N-dimethyl-formamide at 20℃; for 12 h;
To a solution of 4-hydroxyphenylboronic acid (1.0 equiv., 5 mmol) in dry DMF (0.05 M) was added imidazole (5.0 equiv.) at rt, followed by the addition of TBSCl (3.5 equiv.). The reaction mixture was stirred at rt for 12 h; after completion monitored by TLC, the mixture was extracted with ethyl acetate (330 mL) and water (50 mL), and the organic layers were dried over MgSO4 and concentrated under vacuum. The residue was purified by flash chromatography (hexane/ethyl acetate 10 : 1 → 3 : 1) to give the product as a white solid (2.27 g, 90percent yield). Rf (hexane/ethyl acetate 1 : 1) 0.30. δH (300 MHz, CDCl3) 8.11 (2H, d, J 8.4), 6.96 (2H, d, J 8.4), 1.02 (9H, s), 0.26 (6H, s). δC (75 MHz, CDCl3) 159.9, 137.6, 119.9, 111.0, 25.8, 18.4, 4.2. The spectroscopic data matched those reported in the literature.[15]
90%
With 1H-imidazole In N,N-dimethyl-formamide at 0 - 25℃; for 12 h; Inert atmosphere
General procedure: The compounds could be prepared according to the literature.40 Toa solution of hydroxy substrate (1.0 equiv.) in anhydrous DMF (0.05 M)was added imidazole (2.5 or 5.0 equiv.) at 0 °C, followed by the additionof TBSCl (1.5 or 3.5 equiv.). The reaction mixture was allowed towarm to RT for 12 h. After completion monitored by TLC, the mixturewas extracted with ethyl acetate (3×30 mL) and H2O (50 mL), theorganic layers were dried over MgSO4 and concentrated in vacuo.
60.2%
With 1H-imidazole In N,N-dimethyl-formamide at 20℃;
1) Synthesis of 4-(tert-butyldimethylsilyloxy)phenylboronic acid; A solution of 4-hydroxyphenylboronic acid (1 g, 7.25 mmol), tert-butyldimethylsilyl chloride (3.28 g, 21.76 mmol) and imidazole (2.47 g, 36.3 mmol) in DMF was stirred overnight at room temperature. The reaction mixture was diluted with ethyl acetate, washed with saturated sodium hydrogen carbonate solution, then dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The resulting residue was purified by silica gel flash column chromatography (developing solvent = ethyl acetate:n-hexane (1:1)), to thereby obtain the titled compound (1.1 g, 60.2percent). 1H-NMR (CD3OD) δ: 0.21 (6H, s), 0.99 (9H, s), 6.83 (2H, d, J=8.4 Hz), 7.54 (2H, d, J=8.4 Hz).
60.2%
With 1H-imidazole In N,N-dimethyl-formamide at 20℃;
1) Synthesis of 4-(tert-butyldimethylsilyloxy)phenylboronic acid A solution of 4-hydroxyphenylboronic acid (1 g, 7.25 mmol), tert-butyldimethylsilyl chloride (3.28 g, 21.76 mmol) and imidazole (2.47 g, 36.3 mmol) in DMF was stirred overnight at room temperature. The reaction mixture was diluted with ethyl acetate, washed with saturated sodium hydrogen carbonate solution, then dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The resulting residue was purified by silica gel flash column chromatography (developing solvent=ethyl acetate:n-hexane (1:1)), to thereby obtain the titled compound (1.1 g, 60.2percent). 1H-NMR (CD3OD) δ: 0.21 (6H, s), 0.99 (9H, s), 6.83 (2H, d, J=8.4 Hz), 7.54 (2H, d, J=8.4 Hz).
Reference：
[1] Australian Journal of Chemistry, 2018, vol. 71, # 10, p. 789 - 797
[2] Bioorganic and Medicinal Chemistry, 2018, vol. 26, # 22, p. 5852 - 5869
[3] Patent: EP2048153, 2009, A1, . Location in patent: Page/Page column 46
[4] Patent: US2011/275703, 2011, A1, . Location in patent: Page/Page column 35
[5] Organic Letters, 2011, vol. 13, # 19, p. 5314 - 5317
3
[ 5419-55-6 ]
[ 67963-68-2 ]
[ 159191-56-7 ]
Yield
Reaction Conditions
Operation in experiment
20.9 g
Stage #1: With hydrogenchloride; n-butyllithium In tetrahydrofuran; hexane at -78℃; Inert atmosphere Stage #2: With Triisopropyl borate In tetrahydrofuran; hexane at -78 - 20℃; for 13 h; Inert atmosphere Stage #3: With hydrogenchloride In tetrahydrofuran; hexaneInert atmosphere
Under an argon atmosphere, to a solution of (4-bromophenoxy)(tert-butyl)dimethylsilane (36) (32.3 g, crude) prepared above in anhydrous THF (300 mL) was added n-butyl lithium (2.64 M n-hexane solution) (46.0 mL, 121 mmol) at -78° C., and the mixture was stirred for an hour. To this was added triisopropyl borate (134 mL, 579 mmol) at the same temperature and the mixture was stirred for 13 hours while elevating to room temperature. To the mixture was added 1 M hydrochloric acid (200 mL) and the product was extracted with ethyl acetate (200 mL*3). The combined organic extract was washed successively with water (300 mL) and brine (200 mL), followed by drying over anhydrous sodium sulfate. After filtration and concentration under reduced pressure, the residue was recrystallized (n-hexane/ethyl acetate) to give Compound 37 (20.9 g, 82.9 mmol, 71.8percent (2 steps)) as a colorless solid. Rf=0.62 (n-hexane/ethyl acetate=1/1); 1H NMR (400 MHz, CDCl3) δ 0.25 (s, 6H), 1.01 (s, 9H), 6.93-6.98 (AA'BB', 2H), 8.09-8.14 (AA'BB', 2H).
Preparation 86 To a solution of 4-tert-butyldimethylsilyloxybromobenzene (11.49 g) in tetrahydrofuran (100 ml) was added a solution of n-butyllithium in n-hexane (1.59M, 32.7 ml) dropwise at -55 C. under a nitrogen atmosphere, and the mixture was stirred for 1 hour at -60 C. To the reaction mixture was added triisopropyl borate (12.84 ml), and the mixture was stirred at -60 C. for 1 hour. The reaction mixture was warmed to ambient temperature, poured into a saturated aqueous ammonium chloride solution and extracted with ethyl acetate. The separated organic layer was washed with brine, dried over magnesium sulfate and evaporated under reduced pressure. The solid was triturated with n-hexane, filtered and washed with n-hexane to give 4-tert-butyldimethylsilyloxyphenylboronic acid (7.45 g). 1H-NMR (CDCl3): delta0.23(6H,s), 1.01(9H,s), 6.94(2H,d,J=8.5 Hz), 8.10(2H,d,J=8.5 Hz)
With hydrogenchloride; n-butyllithium; In tetrahydrofuran; hexane;
Reference Synthesis Example 2 4-(tert-Butyldimethylsilyloxy)phenylboronic acid (37) (known compound, Reference: P. Jeanjot, et al., Synthesis, 513-522 (2003)) Under an argon atmosphere, to a solution of (4-bromophenoxy)(tert-butyl)dimethylsilane (36) (32.3 g, crude) prepared above in anhydrous THF (300 mL) was added n-butyl lithium (2.64 M n-hexane solution) (46.0 mL, 121 mmol) at -78 C., and the mixture was stirred for an hour. To this was added triisopropyl borate (134 mL, 579 mmol) at the same temperature and the mixture was stirred for 13 hours while elevating to room temperature. To the mixture was added 1 M hydrochloric acid (200 mL) and the product was extracted with ethyl acetate (200 mL*3). The combined organic extract was washed successively with water (300 mL) and brine (200 mL), followed by drying over anhydrous sodium sulfate. After filtration and concentration under reduced pressure, the residue was recrystallized (n-hexane/ethyl acetate) to give Compound 37 (20.9 g, 82.9 mmol, 71.8% (2 steps)) as a colorless solid. Rf=0.62 (n-hexane/ethyl acetate=1/1); 1H NMR (400 MHz, CDCl3) delta 0.25 (s, 6H), 1.01 (s, 9H), 6.93-6.98 (AA'BB', 2H), 8.09-8.14 (AA'BB', 2H).
20.9 g
Under an argon atmosphere, to a solution of (4-bromophenoxy)(tert-butyl)dimethylsilane (36) (32.3 g, crude) prepared above in anhydrous THF (300 mL) was added n-butyl lithium (2.64 M n-hexane solution) (46.0 mL, 121 mmol) at -78 C., and the mixture was stirred for an hour. To this was added triisopropyl borate (134 mL, 579 mmol) at the same temperature and the mixture was stirred for 13 hours while elevating to room temperature. To the mixture was added 1 M hydrochloric acid (200 mL) and the product was extracted with ethyl acetate (200 mL*3). The combined organic extract was washed successively with water (300 mL) and brine (200 mL), followed by drying over anhydrous sodium sulfate. After filtration and concentration under reduced pressure, the residue was recrystallized (n-hexane/ethyl acetate) to give Compound 37 (20.9 g, 82.9 mmol, 71.8% (2 steps)) as a colorless solid. Rf=0.62 (n-hexane/ethyl acetate=1/1); 1H NMR (400 MHz, CDCl3) delta 0.25 (s, 6H), 1.01 (s, 9H), 6.93-6.98 (AA'BB', 2H), 8.09-8.14 (AA'BB', 2H).
With sodium acetate; acetic acid;palladium diacetate; antimony(III) chloride; at 25℃; for 24h;
Palladium (II) acetate (0.23 g, 0.1 eq) and antimony (III) chloride (0 23 g, 0 1 eq) are added to a solution of 80 mL acetic acid containing 2-cyclopenten-l-one, 2, (0.82 g, 10 mmol), sodium acetate (1.6 g, 20 mmol) and 4-tertbutyldimethyylsilyloxyphenyl boronic acid, 4, (2.54 g, 10 mmol) under nitrogen The reaction is stirred for 24 hours at 250C, the black precipitate is filtered off and the filtrate diluted with 250 mL of brine, then extracted twice with 50 mL of methylene chloride The organic layer is stirred with saturated bicarbonate solution for 30 minutes, washed with brine and dried over magnesium sulfate. The solvent is removed and chromatographed to provide 3-(4'- hydroxyphenyl)cyclopentanone.
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