* 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.
Reference：
[1] Angewandte Chemie - International Edition, 2010, vol. 49, # 24, p. 4071 - 4074
[2] Organic Letters, 2013, vol. 15, # 14, p. 3734 - 3737
[3] Organic Letters, 2015, vol. 17, # 23, p. 5934 - 5937
[4] Chemistry - A European Journal, 2013, vol. 19, # 6, p. 2131 - 2141
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[ 202925-08-4 ]
[ 850793-25-8 ]
Reference：
[1] Journal of the American Chemical Society, 2016, vol. 138, # 41, p. 13493 - 13496
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[ 202925-08-4 ]
[ 202982-70-5 ]
Yield
Reaction Conditions
Operation in experiment
88%
Stage #1: With boron tribromide In dichloromethane at -70 - 20℃; for 0.25 h; Stage #2: With water; sodium hydrogencarbonate In dichloromethane at 20℃;
Intermediate 16; 3-Chloro -5-fluorophenol. A solution of 3-chloro-5-fiuoroanisole (10 g, 62 mmol) in CH2CI2 (50 mL) was cooled in a stream of argon to -70 0C under stirring. BBr3 (11.8 mL, 124 mmol) was added dropwise under vigorous stirring at -70 0C in 15 min. The reaction mixture was heated to room temperature and alkalized with the saturated NaHCO3 solution to pH -6. The layers were separated, and the water layer was extracted with CH2CI2 (2x50 mL). The combined organic layer was washed with brine, dried over Na2SO4 and evaporated in vacuo to give the title compound (8 g, 88percent, 54.6 mmol) as a yellow oil. 1H NMR data (dmso-d6): 10.36 (s, 1H, OH), 6.73 - 6.79 (m, 1H, H-Ar), 6.64 - 6.68 (m, 1 H, H-Ar), 6.53 - 6.59 (m, 1H, H-Ar).
Intermediate 16; 3-Chloro -5-fluorophenol. A solution of 3-chloro-5-fiuoroanisole (10 g, 62 mmol) in CH2CI2 (50 mL) was cooled in a stream of argon to -70 0C under stirring. BBr3 (11.8 mL, 124 mmol) was added dropwise under vigorous stirring at -70 0C in 15 min. The reaction mixture was heated to room temperature and alkalized with the saturated NaHCO3 solution to pH -6. The layers were separated, and the water layer was extracted with CH2CI2 (2x50 mL). The combined organic layer was washed with brine, dried over Na2SO4 and evaporated in vacuo to give the title compound (8 g, 88percent, 54.6 mmol) as a yellow oil. 1H NMR data (dmso-d6): 10.36 (s, 1H, OH), 6.73 - 6.79 (m, 1H, H-Ar), 6.64 - 6.68 (m, 1 H, H-Ar), 6.53 - 6.59 (m, 1H, H-Ar).
With bis[chloro(1,2,3-trihapto-allylbenzene)palladium(II)]; N-[2-(di(1-adamantyl)phosphino)phenyl]morpholine; hydrazine hydrate; sodium t-butanolate; In toluene; at 90℃; for 1h;Inert atmosphere; Glovebox;
In an inert atmosphere glovebox, [Pd(cinnamyl)Cl]2 (typically 2.5 mol%) and Mor-DalPhos(typically 7.5 mol%) were added to a vial sealed with a cap containing a PTFE septum and stirred in toluene for 5 min, then NaOtBu (2.1 equiv.) was added along with the aryl chloride substrate (1 equiv., [ArCl] = 0.1 M) if it was a solid. After removing the vial from the glovebox the aryl chloride was added via a syringe if it was a liquid, along with hydrazine hydrate (2.0 equiv.). The reaction was stirred at the desired temperature for 0.5-2 h. Generally, after a short period of time, reactions were observed to darken and considerable black precipitate was formed.After completion of the reaction was observed by thin layer chromatography (TLC) or GC methods, the solution was allowed to cool and filtered through a short plug of neutral alumina, which was washed with CH2Cl2/MeOH (25:1). The resulting eluent solution was concentrated and charged with ethyl acetoacetate (1 equiv., [ethyl acetoacetate] = 0.125 M) and glacial acetic acid. The solution was heated at reflux for 0.5-3 h, and the reaction progress was monitored by use of TLC or GC methods. After complete consumption of the aryl hydrazine, the reaction was cooled, diluted with EtOAc (40 mL) and washed with H2O (60 mL) followed by 1:1 water/brine (60 mL). The organic fractions were dried over Na2SO4, filtered and concentrated to afford crude product which was purified by column chromatography. Typical reaction scales were 0.4 -1.0 mmol. Aryl hydrazines were stored at -4 C for no longer than 12 hours before reacting with ethyl acetate.
With palladium diacetate; caesium carbonate; 4,5-bis(diphenylphos4,5-bis(diphenylphosphino)-9,9-dimethylxanthenephino)-9,9-dimethylxanthene; In 1,4-dioxane; at 110℃; for 15h;Inert atmosphere;
General procedure for coupling reaction: An oven-dried resealable Schlenk tube were charged with Pd(OAc)2 (6.7 mg, 0.03 mmol), Xantphos (34.7 mg, 0.06 mmol), 2-methylpropane-2-sulfinamide (145 mg, 1.2 mmol) and Cs2CO3 (650 mg, 2.0 mmol). The Schlenk tube was evacuated and back-filled with argon. 4-bromo-2-methylbenzonitrile (196 mg, 1.0 mmol) and dioxane (3 ml) were added and the Schlenk tube was then sealed with a Teflon screw cap and placed in a preheated oil bath at 100oC for 15 h. After cooling of the reaction mixture to room temperature, water was added and the reaction mixture was extracted with ethyl acetate. The combined organic layer was washed with brine, dried over Na2SO4, filtered, and concentrated under vacuum. The product was purified by flash chromatography. Yield: 228 mg, 97 % [table-1, entry-5].
A mixture of aluminum chloride (2.50 g, 18.7 mmol) and acetyl chloride (1.30 rnL, 18.7 mmol) in CH2Cl2 (10.0 mL) was stirred at 0 C for 30 min. The reaction mixture was slowly added with <strong>[202925-08-4]1-chloro-3-fluoro-5-methoxybenzene</strong> (13-1, 1.00 g, 6.23 mmol) in CH2Cl2 (5.0 mL). The solution was stirred at room temperature for additional 2.0 h. The solution was bsified with saturated aqueous NaHCO3, and the organic layer was separated,dried over MgSO4(s), and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel to give a mixture of 1-(2-chloro-6-fluoro-4-methoxyphenyl)ethanone (13-2) and 1-(2-chloro-4-fluoro-6-methoxyphenyl)ethanone (13-3) as yellow oil in 1.2 g (5.9 mmol) total weight (95% yield).
With 1-fluoro-2,4,6-trimethylpyridinium hexafluorophosphate; (tBuCN)2Cu*OTf; silver fluoride; In tetrahydrofuran; at 80℃; for 18h;Inert atmosphere;
General procedure: To an oven-dried 4 mL vial was added arene (0.1 mmol, 1.0 equiv), and 0.2 mL of a stock solution containing 0.1 mol% [Ir(COD)OMe]2, 0.2 mol% 4,4'-di-tert-butyl bipyridine (dtbpy), and 0.75 equiv of B2P i2. The vial was sealed with a Teflon-lined cap and heated at 80 C for 18 h. The solution was allowed to cool, and the volatile components were removed in vacuo. To the crude ArBPin was added AgF (25 mg, 0.2 mmol, 2.0 equiv), ('BuCN^CuOTf (76 mg, 0.2 mmol, 2.0 equiv), Me3pyF-PF6 (86 mg, 0.3 mmol, 3.0 equiv) and THF (2.0 mL). The vial was sealed with a Teflon-lined cap and heated at 50 C with vigorous stirring for 18 h. The solution was allowed to cool to room temperature, and 1 1.0 (0.1 mmol, 1.0 equiv) of l-bromo-4-fluorobenzene was added as an internal standard. The crude reaction mixture was analyzed by 19F NMR spectroscopy to determine the yield of aryl fluoride. 19F NMR chemical shifts were compared to authentic samples of the aryl fluoride product to confirm the identity of the product, and the identities of the products were further confirmed by GC/MS.; rfThe fluorination reaction was performed at 80 C for 18 h.
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[ 202925-08-4 ]
[ 121-43-7 ]
(4-chloro-2-fluoro-6-methoxyphenyl)boronic acid[ No CAS ]
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