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...presented by the following formula (4) which can respectively correspond to the formula (1) can be obtained. (D) Fluorine substituted aromatic compound represented by the formula (4) corresponding to the hydroxy compound wherein X1 is a substituent of the group (a) in the formula(1): ... 2-fluorobenzophenone, 3-fluorobenzophenone, 4-fluorobenzophenone, 2-trifluoromethylfluorobenzene, 3-trifluoromethylfluorobenzene, 4-trifluoromethylfluorobenzene, 2-trichloromethylfluorobenzene, 3-trichloromethylfluorobenzene, 4-trichloromethylfluorobenzene, 2-trifluoromethoxyfluorobenzene, 3-trifluoromethoxyfluorobenzene, 4-trifluoromethoxyfluorobenzene, 2-trichloromethoxyfluorobenzene, 3-trichloromethoxyfluorobenzene, 4-trichloromethoxyfluorobenzene, 2-fluorophenylmethylsulfone, 3-fluorophenylmethylsulfone, ...
2
[ 1077-01-6 ]
[ 866632-57-7 ]
Yield
Reaction Conditions
Operation in experiment
To the solution of 3- (trifluoromethoxy)fluorobenzen(1g, 5.5 mmol) in lOmL THF at -78C, n-BuLi (1.6M, 3.75mL) was added dropwise. The resulting solution was stirred at -78C for 30 min. 12 (2.1g, 8.25 mmol) in THF (5mL) was added. The mixture was warmed to room temperature and then quenched with Na2C03 in saturated Na2S203 (1: 10) (30mL). The crude product was extracted with ether. The ether layer was dried over Na2S04 and filtered through a short silica gel column to give the desired iodide as an oil. ¹H NMR (CDC13): 7.39 (m, 1H), 7.12 (d, J=9.0 Hz, 1H), 7.05 (t, J=6.0 Hz, 1H) MS (ESI): m/e 307 (M+1)+
To a solution of l-fluoro-3-trifluoromethoxy-benzene (1.73g, 9.6 mmol) inTHF (20 mL) at -78 0C was added nBuLi (1.2eq, 4.6 mL of 2.5M in hexanes). The mixture was stirred for 180 minutes and quenched with DMF (2 mL) and allowed to warm to room temperature. Solvents were removed, the reaction was washed with H2O (10 mL) and the organics concentrated giving the crude product.
4-Fluoro-2-trifluoromethoxy-benzaldehyde To a solution of <strong>[1077-01-6]1-fluoro-3-trifluoromethoxy-benzene</strong> (1.73g, 9.6 mmol) in THF (20 mL) at -78 C. was added nBuLi (1.2 eq, 4.6 mL of 2.5M in hexanes). The mixture was stirred for 180 minutes and quenched with DMF (2 mL) and allowed to warm to room temperature. Solvents were removed, the reaction was washed with H2O (10 mL) and the organics concentrated giving the crude product.
With sulfuric acid; potassium nitrate; at 0 - 5℃; for 2h;Inert atmosphere;
<strong>[1077-01-6]1-fluoro-3-(trifluoromethoxy)benzene</strong> (7.5 g, 41.6 mmol) was dissolved in concentrated sulfuric acid (30 mL),and the mixuture was cooled to 0 C. KNO3 (1.04 g, 10.25 mmol) was added slowly in batches. The internal temperatureis keeped below 5 C. Upon completion of the addition, the mixture was stirred for 2 hours. An eice-water mixture (about50 mL) was added. The reaction solution was extracted with methyl tert-butyl ether (2033 mL), and the organic phaseswere combined, dried and filtered. The filtrate was concentrated and purified by flash silica gel column chromatographyto obtain 4-fluoro-1-nitro-2-(trifluoromethoxy)benzene (4.0 g, 42%).
16%
With sulfuric acid; nitric acid; at -10℃;
(Comparative Example 6); 4-Fluoro-l-nitro-2- (trifluoromethoxy) benzeneFuming nitric acid (20 mL) was added dropwise to concentrated sulfuric acid (40 ml) under cooling (-100C), and subsequently, 1- fluoro-3- (trifluoromethoxy) benzene (15 g, 83 mmol) was added to the mixture at -100C, and the mixture was stirred for 0.5 hours. After the mixture was added into ice-water to stop the reaction, it was extracted with dichloromethane . After the obtained organic layer was washed with a IN aqueous sodium hydroxide solution and water, it was dried with anhydrous sodium sulfate. After filtration, the solution was concentrated and the residue was purified by silica gel column chromatography (100:0-97:3, hexane : ethyl acetate) to give the title compound (3.1 g, 16%) as an oil.1H-NMR (400 MHz, CDCl3) delta: 8.10 (IH, dd, J = 5.5, 9.4 Hz) , 7.23-7.15 (2H, m) .
12 g
With sulfuric acid; potassium nitrate; at 0℃; for 3h;Cooling with ice;
Under ice cooling mixture of 3-fluoro - trifluoromethoxyphenyl (20g) was dissolved in 40 ml of concentrated sulfuric acid, with rapid stirringWas added portionwise potassium nitrate (28g), was stirred at 0oC 3 hours and stirred at room temperature overnight, the reaction solution was carefullyGo on into 1 kg ice, stirred for 30 minutes, extracted with ethyl acetate, dried over sodium sulfate, filtered, and the filtrate was evaporated, the residue was purified by column chromatography to give 12 g pale yellow liquid.
0.5 g
With sulfuric acid; nitric acid; at -10 - 20℃; for 0.5h;
To a 100 mL round-bottomed flask were added concentrated H2SO4 (25 mL), fuming HNO3 (25 mL), and <strong>[1077-01-6]1-fluoro-3-(trifluoromethoxy)benzene</strong> (9.0 g, 50 mmol) at -10 C. in sequence. The mixture was stirred at rt for 30 min then poured onto ice and extracted with EtOAc (3*20 mL). The combined organic layers were washed with saturated aqueous NaHCO3 solution (30 mL), brine (30 mL), dried over anhydrous Na2SO4, concentrated to dryness, and purified by FCC to give the title compound as a pale-yellow oil (0.50 g). 1H NMR (300 MHz, CDCl3): delta 8.21-8.14 (m, 1H), 7.21-7.12 (m, 2H).
8.5 g
With sulfuric acid; potassium nitrate; at -5 - 0℃; for 1h;
Add 20 mL of concentrated sulfuric acid to a 250 mL three-necked flask.The ice salt bath is cooled to -5-0 C,Adding m-fluorotrifluoromethoxybenzene(10 g, 60 mmol), then potassium nitrate (5.9 g, 60 mmol) was added portionwise.The reaction was stirred at 0 C for 1 h.Slowly pour the reaction into the iceIn water, extracted with ethyl acetate (40 mL×3) three times, and the organic phases were combined.Wash 3 times with saturated saline (20mL × 3),Dry over anhydrous sodium sulfate for 0.5 h, suction filtration under reduced pressure.The filtrate was concentrated under reduced pressure at 45 C to give 8.5 g of pale yellow oil.
11A) 4-Fluoro-1-nitro-2-trifluoromethoxy-benzene To 1-fluoro-3-trifluoromethoxybenzene (1 mL) was added concentrated sulfuric acid (1 mL) at 0 C. To the cold solution was added dropwise (0.7 mL) of a solution made from concentrated nitric acid (1 mL) and concentrated sulfuric acid (1 mL). The reaction was slowly allowed to warm to room temperature then poured onto ice and extracted with ether. The organic layer was separated and washed with sodium hydroxide 1N, then brined and dried over magnesium sulfate. The solvent was removed under reduce pressure at room temperature. A pale yellow oil (1 g) was recovered and used without further purification.
General procedure: To reactant 1 or 3 (1 g, 8.76 mmol) in THF (50 ml), was added LDA (condition A) or n-BuLi (condition B) (4.82 ml, 9.64 mmol) at -78 C slowly, after 30 min, added EtO-13CHO/DMF-13CHO (0.736 ml, 9.64 mmol) and left for stirring at -78 C for 30 min. Quenched with a few drops of dil H2SO4 (aq) and satd NH4Cl (aq 50 mL), extracted with Et2O (3 × 50 mL), dried, purified by column chromatography on silica gel eluting with a solution of EtOAc/hexane(1:9) to give products 2 or 4 (0.860 g, 69% yield).
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