* 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] Journal of Organic Chemistry, 2008, vol. 73, # 5, p. 1925 - 1934
2
[ 455-93-6 ]
[ 403-19-0 ]
Reference：
[1] Journal of the Chemical Society, 1949, p. 642,645
3
[ 321-28-8 ]
[ 454-16-0 ]
[ 455-93-6 ]
[ 484-94-6 ]
Reference：
[1] Journal of Organic Chemistry, 1998, vol. 63, # 23, p. 8448 - 8454
[2] Journal of Organic Chemistry, 1998, vol. 63, # 23, p. 8448 - 8454
4
[ 100-17-4 ]
[ 455-93-6 ]
Yield
Reaction Conditions
Operation in experiment
73%
With xenon difluoride; boron trifluoride diethyl etherate In acetonitrile at -35 - 20℃; for 2.5 h; Inert atmosphere
General procedure: A three-necked flask equipped with an argon inlet and thermometer was loaded with arene 1 or 3—8 (10 mmol) in dry MeCN (15 mL). Then, BTFE (2.0 g, 14 mmol) was added. The mixture was cooled in the argon stream down to –35 °C and XeF2 (2.05 g, 12.5 mmol) was added in small portions. The mixture was warmed to –25 °C, stirred for 30 min at this temperature, then heated to 20 °C for 1 h, and stirred for additional 1 h (GLC control). A saturated solution of sodium bicarbonate was added to the reaction mass until termination of gas evolution. The resulted mixture was extracted with diethyl ether (3×20 mL). The extract was washed with water and dried with sodium sulfate. In the case of benzene (1), toluene (3), and chlorobenzene (4), the diethyl ether extracts were subjected to molecular distillation and fractionated, each fraction was analyzed by GLC and NMR spectroscopy. In the case of bromobenzene (5), nitrobenzene (6), p-nitrotoluene (7), and p-nitroanisole (8), the ethereal extracts were evaporated in vacuo at the temperature below 25 °C, the residue was dissolved in chloroform and subjected to flash chromatography (the eluent was hexane—chloroform, 3 : 1). The eluent was concentrated under normal pressure and the residue was analyzed by NMR spectroscopy. In the case of iodobenzene (15), a precipitate formed upon neutralization with a solution of sodium bicarbonate was filtered, washed with water, sequentially with MeCN (5 mL) and Et2O (5 mL) preserving the filtrate, and dried in air to yield a solid residue (1.1 g), which according to the NMR spectral data was a mixture consisting of (based on the weight percentages) 76percent of iodosobenzene (16) and 24percent of (4-iodophenyl)phenyliodonium tetrafluoroborate (17). Evaporation of the organic filtrate followed by the treatment of the residue with CHCl3 affords 100 mg of compound 18 with m.p. 149 °C (cf. Ref. 17: 147—149 °C).
Reference：
[1] Russian Journal of Organic Chemistry, 2013, vol. 49, # 9, p. 1287 - 1290[2] Zh. Org. Khim., 2013, vol. 49, # 9, p. 1287 - 1290,4
[3] Russian Chemical Bulletin, 2015, vol. 64, # 5, p. 1049 - 1052[4] Izv. Akad. Nauk, Ser. Khim., 2015, # 5, p. 1049 - 1052,4
[5] Journal of Organic Chemistry, 1984, vol. 49, p. 806 - 813
[6] Journal of Organic Chemistry, 1981, vol. 46, # 22, p. 4629 - 4631
5
[ 67-56-1 ]
[ 369-34-6 ]
[ 455-93-6 ]
Yield
Reaction Conditions
Operation in experiment
91%
at 10 - 20℃; for 2 - 3 h;
Step 4: Preparation of 3-fluoro-4-methoxyaniline (8) Metallic sodium (1.45 grams, 63 mmol) was added slowly and portion wise to pre cooled (10° C.) methanol (100 mL) with stirring under nitrogen atmosphere. The mixture was stirred at room temperature until all the sodium metal gets dissolved. To this was added 3,4-difluoro nitrobenzene (6) (10 grams, 63 mmol) at room temperature and stirring continued at the same temperature for 2-3 hours. The mixture was then concentrated under vacuum and poured into ice-water (100 mL). The pH of the mixture was adjusted to ~7 by adding 2N HCl with stirring. The solid separated was filtered off, washed with water and dried under vacuum to afford the product 2-fluoro-4-nitroanisol (7) (9.75 grams). Yield: 91percent; Melting point: 102-104° C.
64%
With potassium hydroxide In dimethyl sulfoxide at 20℃; for 16 h;
General procedure: A mixture of 2-fluorobenzamide (1a, 69.5 mg, 0.5 mmol), MeOH (ca. 32.0 mg, 1.0 mmol), KOH (56.0 mg, 1.0 mmol) and DMSO (2.0 mL) in a 25 mL screw-capped thick-walled Pyrex tube was stirred at room temperature for 16 h, and then water (10 mL) was added to the reaction mixture with stirring, and the mixture was extracted with ethyl acetate three times (3 * 10 mL). The combined organic phases were dried over Na2SO4 overnight. The filtered solution was concentrated under reduced pressure, and the crude residue was purified by column chromatography on silica gel with the use of petroleum ether/ethyl acetate/trimethylamine (gradient mixture ratio from 6:1:0.05 to 2:1:0.05 in volume) to afford 2aa as a white solid in 80percent yield (60.7 mg).
57%
With sodium hydroxide In dimethyl sulfoxide at 20℃; for 12 h;
3,4-difluoronitrobenzene (31.88, 0.2111001), high purity NaOH (168,0.4111001), methanol (88,0.25mo 1), DMSO (200 mL) was added to the reactor and the reaction was stirred at 20 ° C for 12 hours. After completion of the reaction, 800 mL of ethyl acetate was added to the system and diluted 5 times with 200 mL of saturated brine. The organic phase was separated and dried over anhydrous sodium sulfateAfter which it was filtered, evaporated to dryness, and then it was loaded onto a silica gel column to separate petroleum ether: ethyl acetate = 4: 1 (volume) Was eluted as an eluent until the product appeared, the solution containing the product was collected and evaporated to dryness. After drying with a vacuum chestnut, 3-fluoro-4-methoxy nitrobenzene pure product, the yield of 57percent.
Reference：
[1] Patent: US2006/128729, 2006, A1, . Location in patent: Page/Page column 77
[2] Tetrahedron, 2018, vol. 74, # 2, p. 303 - 307
[3] Patent: CN106565522, 2017, A, . Location in patent: Paragraph 0037; 0038
[4] Russian Chemical Bulletin, 2006, vol. 55, # 7, p. 1243 - 1247
6
[ 321-28-8 ]
[ 455-93-6 ]
Reference：
[1] Journal of Medicinal Chemistry, 2000, vol. 43, # 24, p. 4701 - 4710
[2] Journal of the Chemical Society, 1926, p. 1332
[3] Chemische Berichte, 1933, vol. 66, p. 1180,1183
[4] Journal of the American Chemical Society, 1946, vol. 68, p. 1583[5] Chem.Abstr., 1947, p. 6274
[6] Journal of the American Chemical Society, 1941, vol. 63, p. 609
[7] Journal of the Chemical Society, Perkin Transactions 2: Physical Organic Chemistry (1972-1999), 1980, p. 832 - 834
[8] Patent: US4431807, 1984, A,
7
[ 100-17-4 ]
[ 455-93-6 ]
[ 392-25-6 ]
Reference：
[1] Journal of Fluorine Chemistry, 2007, vol. 128, # 1, p. 29 - 33
[2] Journal of the Chemical Society, Chemical Communications, 1995, # 1, p. 17 - 18
[3] Journal of Fluorine Chemistry, 2000, vol. 102, # 1-2, p. 169 - 173
8
[ 403-20-3 ]
[ 455-93-6 ]
Reference：
[1] Journal of Organic Chemistry, 2015, vol. 80, # 21, p. 10498 - 10504
Reference：
[1] Chemische Berichte, 1933, vol. 66, p. 1180,1183
[2] Journal of the Chemical Society, 1926, p. 1332
[3] Journal of the Chemical Society, 1940, p. 810
[4] Journal of the American Chemical Society, 1940, vol. 62, p. 350,353
18
[ 321-28-8 ]
[ 7697-37-2 ]
[ 344-78-5 ]
[ 455-93-6 ]
Reference：
[1] Chemische Berichte, 1933, vol. 66, p. 1180,1183
[2] Journal of the Chemical Society, 1926, p. 1332
[3] Journal of the Chemical Society, 1940, p. 810
Reference：
[1] Journal of the Chemical Society, 1949, p. 642,645
21
[ 455-93-6 ]
[ 366-99-4 ]
Yield
Reaction Conditions
Operation in experiment
98%
With palladium on activated charcoal In ethyl acetate at 20℃; for 1 h;
3-Fluoro-4-methoxy-nitrobenzene (0.5 g, 2.9 mmol) was dissolved in ethyl acetate (10 mL) was added palladium on carbon (50 mg), stirred at room temperature for 1 hour. The reaction mixture was filtered, the filtrate was concentrated to give the title compound 3-fluoro-4-methoxyaniline (7B), an off-white solid (0.4 g, 98percent yield).
91%
With hydrogen In ethanol at 20℃; for 4 h;
To a mixture of 10percent Pd/C (1.5 grams) in ethanol (150 mL) taken in a Parr.(TM). hydrogenation flask was added a solution of 2-fluoro-4-nitroanisole (7) (9.09 grams, 53 mmol) in ethanol (150 mL) slowly. The mixture was then stirred under hydrogen atmosphere (40 psi) for 4 hours at room temperature. After completion of the reaction the mixture was filtered through Celite.(TM). and the residue was washed thoroughly using ethanol (20 mL). The filtrates and washings were collected, combined and evaporated to dryness. The solid obtained was stirred in hexane (50 mL) for 1 hour and filtered to give the desired product 3-fluoro-4-methoxyaniline (8) (6.75 grams).
78%
With zinc In water at 20℃; for 0.0833333 h; Inert atmosphere
General procedure: Under an argon atmosphere, a nitro group-containing compound (0.237 mmol) was weighed into a 5 mL microwave vial containing a magnetic stir bar and a Teflon-lined septum. Subsequently zinc dust (155 mg, 2.37 mmol), ammonium chloride (25 mg, 0.475 mmol) and the aqueous oligosaccharide solution (2 wt percent HPMC, 40-60 cps, in degassed Millipore water) were added and the reaction mixture was vigorously stirred at the indicated temperature for the indicated time. The reaction mixture was diluted with ethyl acetate, the solids were filtered and the aqueous phase was extracted 3x with ethyl acetate. The combined organic extracts were dried with magnesium sulfate, filtered and concentrated in vacuo. The crude product was purified by flash chromatography on silica gel.; Following the general procedure using 2-fluoro-4-nitroanisole (171 mg, 1.00 mmol), zinc (327 mg, 5.00 mmol), ammonium chloride (64 mg, 1.20 mmol) and 2 ml of aqueous oligosaccharide solution (2 wt percent HPMC, 40-60 cps, in degassed Millipore water), the reaction was allowed to stir for 5 min at room temperature. After column chromatography (0-100 percent ethyl acetate - dichloromethane), the product was obtained (110 mg, 78 percent).ESI-MS: m/z (percent): 142.10 (100, [M+H]+).1H NMR (600MHz, d6-OMSO): δ [ppm] : 6.856.31 - 6.28 (m, 1H), 4.91 (sbr, 2H), 3.68 (s, 3H).
Reference：
[1] Journal of Medicinal Chemistry, 2000, vol. 43, # 24, p. 4701 - 4710
[2] Patent: CN104395312, 2016, B, . Location in patent: Paragraph 0640-0645
[3] Patent: US2006/128729, 2006, A1, . Location in patent: Page/Page column 77
[4] Patent: WO2017/129796, 2017, A1, . Location in patent: Page/Page column 251; 252
[5] Journal of the American Chemical Society, 1941, vol. 63, p. 609
[6] Chemische Berichte, 1933, vol. 66, p. 1180,1183
[7] Journal of the American Chemical Society, 1940, vol. 62, p. 350,353
[8] Chemische Berichte, 1937, vol. 70, p. 2396,2400
[9] Journal of the Chemical Society, Perkin Transactions 2: Physical Organic Chemistry (1972-1999), 1980, p. 832 - 834
[10] Patent: US4861799, 1989, A,
2-Fluoro-4-nitroanisole (IX) To a cold (-2), stirred solution of 285 g. (2.26 mol) of 2-fluoroanisole in 1.1 L of acetic anhydride was added, dropwise, 114 mL of fuming nitric acid (sp. gr. 1.59) at such a rate that the reaction temperature remained between -2 and 0. The reaction mixture was stirred for 5 hours at this temperature then poured into 4.0 L of water. The suspension was stirred for 1.5 hours, stored for 15 hours, then extracted with methylene chloride (2*1.0 L). The combined extracts were washed with water (2*500 mL), dried over anhydrous magnesium sulfate, then concentrated in vacuo (475 g.). Crystallization from ethanol gave 147.4 g. (38%) of material suitable for further transformation. Additional material (34.5 g.) was obtained from three scouting runs. Analytically pure product (5.2 g.; 63.4% recovery) was obtained by recrystallizing 8.2 g of the material from 200 mL of ethanol; mp, 105-106 (Literature, R. C. Elderfield et al., J. Am. Chem. Soc., 68, 1584 (1946)). Anal. Calcd for C7 H6 FNO3 (percent): C, 49.13; H, 3.53; F, 11.10; N, 8.19. Found: C, 49.07; H, 3.52; F, 11.02; N, 8.19.
With palladium on activated charcoal; In ethyl acetate; at 20℃; for 1h;
3-Fluoro-4-methoxy-nitrobenzene (0.5 g, 2.9 mmol) was dissolved in ethyl acetate (10 mL) was added palladium on carbon (50 mg), stirred at room temperature for 1 hour. The reaction mixture was filtered, the filtrate was concentrated to give the title compound 3-fluoro-4-methoxyaniline (7B), an off-white solid (0.4 g, 98% yield).
91%
With hydrogen;palladium 10% on activated carbon; In ethanol; at 20℃; under 2068.65 Torr; for 4h;
To a mixture of 10% Pd/C (1.5 grams) in ethanol (150 mL) taken in a Parr hydrogenation flask was added a solution of <strong>[455-93-6]2-fluoro-4-nitroanisole</strong> (7) (9.09 grams, 53 mmol) in ethanol (150 mL) slowly. The mixture was then stirred under hydrogen atmosphere (40 psi) for 4 hours at room temperature. After completion of the reaction the mixture was filtered through Celite and the residue was washed thoroughly using ethanol (20 mL). The filtrates and washings were collected, combined and evaporated to dryness. The solid obtained was stirred in hexane (50 mL) for 1 hour and filtered to give the desired product 3-fluoro-4-methoxyaniline (8) (6.75 grams).
78%
With zinc; In water; at 20℃; for 0.0833333h;Inert atmosphere;
General procedure: Under an argon atmosphere, a nitro group-containing compound (0.237 mmol) was weighed into a 5 mL microwave vial containing a magnetic stir bar and a Teflon-lined septum. Subsequently zinc dust (155 mg, 2.37 mmol), ammonium chloride (25 mg, 0.475 mmol) and the aqueous oligosaccharide solution (2 wt % HPMC, 40-60 cps, in degassed Millipore water) were added and the reaction mixture was vigorously stirred at the indicated temperature for the indicated time. The reaction mixture was diluted with ethyl acetate, the solids were filtered and the aqueous phase was extracted 3x with ethyl acetate. The combined organic extracts were dried with magnesium sulfate, filtered and concentrated in vacuo. The crude product was purified by flash chromatography on silica gel.; Following the general procedure using <strong>[455-93-6]2-fluoro-4-nitroanisole</strong> (171 mg, 1.00 mmol), zinc (327 mg, 5.00 mmol), ammonium chloride (64 mg, 1.20 mmol) and 2 ml of aqueous oligosaccharide solution (2 wt % HPMC, 40-60 cps, in degassed Millipore water), the reaction was allowed to stir for 5 min at room temperature. After column chromatography (0-100 % ethyl acetate - dichloromethane), the product was obtained (110 mg, 78 %).ESI-MS: m/z (%): 142.10 (100, [M+H]+).1H NMR (600MHz, d6-OMSO): delta [ppm] : 6.856.31 - 6.28 (m, 1H), 4.91 (sbr, 2H), 3.68 (s, 3H).
palladium-carbon; In 1,4-dioxane;
[I] 2 g of 5% palladium carbon was added to a solution prepared by dissolving 10 g of <strong>[455-93-6]4-nitro-2-fluoroanisol</strong> in 150 ml of 1,4-dioxane, and the mixture was subjected to catalytic reduction under a hydrogen gas pressure of 4 kg/cm2 at room temperature for 30 minutes. After the completion of the reaction, palladium carbon was removed by filtration, and the solvent was distilled off under reduced pressure to obtain 8.6 g of 4-amino-2-fluoroanisol.
With xenon difluoride; boron trifluoride diethyl etherate; In acetonitrile; at -35 - 20℃; for 2.5h;Inert atmosphere;
General procedure: A three-necked flask equipped with an argon inlet and thermometer was loaded with arene 1 or 3-8 (10 mmol) in dry MeCN (15 mL). Then, BTFE (2.0 g, 14 mmol) was added. The mixture was cooled in the argon stream down to -35 C and XeF2 (2.05 g, 12.5 mmol) was added in small portions. The mixture was warmed to -25 C, stirred for 30 min at this temperature, then heated to 20 C for 1 h, and stirred for additional 1 h (GLC control). A saturated solution of sodium bicarbonate was added to the reaction mass until termination of gas evolution. The resulted mixture was extracted with diethyl ether (3×20 mL). The extract was washed with water and dried with sodium sulfate. In the case of benzene (1), toluene (3), and chlorobenzene (4), the diethyl ether extracts were subjected to molecular distillation and fractionated, each fraction was analyzed by GLC and NMR spectroscopy. In the case of bromobenzene (5), nitrobenzene (6), p-nitrotoluene (7), and p-nitroanisole (8), the ethereal extracts were evaporated in vacuo at the temperature below 25 C, the residue was dissolved in chloroform and subjected to flash chromatography (the eluent was hexane-chloroform, 3 : 1). The eluent was concentrated under normal pressure and the residue was analyzed by NMR spectroscopy. In the case of iodobenzene (15), a precipitate formed upon neutralization with a solution of sodium bicarbonate was filtered, washed with water, sequentially with MeCN (5 mL) and Et2O (5 mL) preserving the filtrate, and dried in air to yield a solid residue (1.1 g), which according to the NMR spectral data was a mixture consisting of (based on the weight percentages) 76% of iodosobenzene (16) and 24% of (4-iodophenyl)phenyliodonium tetrafluoroborate (17). Evaporation of the organic filtrate followed by the treatment of the residue with CHCl3 affords 100 mg of compound 18 with m.p. 149 C (cf. Ref. 17: 147-149 C).
EXAMPLE 9 Fluorination of 4-Nitroanisole By the method outlined in Example 1, 4-nitroanisole was fluorinated to give 2-fluoro-4-nitroanisole (M+ 171, deltaF -131.6 ppm ?CDCl3!, yield 50%) and 2,6-difluoro-4-nitroanisole (M+ 189, deltaF -125.1 ppm ?CDCl3!, yield 20%). Conversion 60%.
Step 4: Preparation of 3-fluoro-4-methoxyaniline (8) Metallic sodium (1.45 grams, 63 mmol) was added slowly and portion wise to pre cooled (10 C.) methanol (100 mL) with stirring under nitrogen atmosphere. The mixture was stirred at room temperature until all the sodium metal gets dissolved. To this was added 3,4-difluoro nitrobenzene (6) (10 grams, 63 mmol) at room temperature and stirring continued at the same temperature for 2-3 hours. The mixture was then concentrated under vacuum and poured into ice-water (100 mL). The pH of the mixture was adjusted to ~7 by adding 2N HCl with stirring. The solid separated was filtered off, washed with water and dried under vacuum to afford the product 2-fluoro-4-nitroanisol (7) (9.75 grams). Yield: 91%; Melting point: 102-104 C.
64%
With potassium hydroxide; In dimethyl sulfoxide; at 20℃; for 16h;
General procedure: A mixture of 2-fluorobenzamide (1a, 69.5 mg, 0.5 mmol), MeOH (ca. 32.0 mg, 1.0 mmol), KOH (56.0 mg, 1.0 mmol) and DMSO (2.0 mL) in a 25 mL screw-capped thick-walled Pyrex tube was stirred at room temperature for 16 h, and then water (10 mL) was added to the reaction mixture with stirring, and the mixture was extracted with ethyl acetate three times (3 * 10 mL). The combined organic phases were dried over Na2SO4 overnight. The filtered solution was concentrated under reduced pressure, and the crude residue was purified by column chromatography on silica gel with the use of petroleum ether/ethyl acetate/trimethylamine (gradient mixture ratio from 6:1:0.05 to 2:1:0.05 in volume) to afford 2aa as a white solid in 80% yield (60.7 mg).
57%
With sodium hydroxide; In dimethyl sulfoxide; at 20℃; for 12h;
3,4-difluoronitrobenzene (31.88, 0.2111001), high purity NaOH (168,0.4111001), methanol (88,0.25mo 1), DMSO (200 mL) was added to the reactor and the reaction was stirred at 20 C for 12 hours. After completion of the reaction, 800 mL of ethyl acetate was added to the system and diluted 5 times with 200 mL of saturated brine. The organic phase was separated and dried over anhydrous sodium sulfateAfter which it was filtered, evaporated to dryness, and then it was loaded onto a silica gel column to separate petroleum ether: ethyl acetate = 4: 1 (volume) Was eluted as an eluent until the product appeared, the solution containing the product was collected and evaporated to dryness. After drying with a vacuum chestnut, 3-fluoro-4-methoxy nitrobenzene pure product, the yield of 57%.
Sodium hydride (60% dispersion in mineral oil; 0.048 g) was added to a stirred solution of tert-butyl 3-hydroxyazetidine-l-carboxylate (Organic Letters 2002, 4, 1859; 0.21 g) in DMF (5 ml) that had been cooled to 50C and the mixture was stirred at 5C for 5 minutes. 2-Fluoro- 4-nitroanisole (0.171 g) was added and the reaction mixture was heated to 6O0C for 3 hours. The resultant mixture was cooled to ambient temperature, acidified to pH6 by the addition of IN aqueous hydrochloric acid solution and extracted with diethyl ether. The organic extract was dried over magnesium sulphate and evaporated. The residue was purified by column chromatography om silica using a 19:1 mixture of methylene chloride and diethyl ether as EPO <DP n="136"/>eluent. There was thus obtained tert-butyl 3-(2-methoxy-5-nitrophenoxy)azetidine- 1-carboxylate as an oil (0.198 g); 1H NMR: (DMSOd6) 139 (s, 9H), 3.84 (m, 2H), 3.93 (s, 3H), 4.34 (m, 2H), 5.14 (m, IH), 7.24 (d, IH), 7.48 (m, IH), 7.95 (m, IH).
With sodium hydroxide; In hydrogenchloride; ethanol; water;
4-Amino-2-fluoroanisole (X) To a cold (5), stirred solution of 776 g. (3.44 mol) of stannous chloride dihydrate in 1500 mL of concentrated hydrochloric acid was added, dropwise, a solution of 147 g. (0.861 mol) of <strong>[455-93-6]2-fluoro-4-nitroanisole</strong> in 3.0 L of ethanol at such a rate that the temperature of the reaction mixture did not exceed 23. The suspension was stirred for 6 hours at room temperature. The ethanol was removed in vacuo at temperatures below 45, and the residue was diluted with 3.0 L of water then basified with 1.0 L of 50% sodium hydroxide. The temperature of the mixture was maintained below 23 during the dropwise addition of the base. The suspension was stirred for 30 minutes then extracted with methylene chloride (1*1.5 L; 2*1.0 L). The combined extracts were washed with water (2*1.0 L), dried over anhydrous magnesium sulfate, then concentrated in vacuo; yield, 110.1 g. (90.2%). The material was suitable for further transformation. Additional product (20.3 g) was obtained from two scouting runs. Analytically pure product (6.5 g.; 74.7% recovery) was obtained by recrystallizing 8.7 g. of the crude product from 50 mL of ethanol; mp, 82-84 (Literature, mp 82.6, G. Shiemann and T. Miau, Ber., 1179 (1933)).
1-fluoro-4-(isocyanomethyl)-2-methoxy-5-nitrobenzene[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
23.21%
With potassium tert-butylate; In N,N-dimethyl-formamide; at -20℃; for 1h;
5(6H)-one: l-Fluoro-4-(isocvanomethyl)-2-methoxy-5-nitrobenzene (96A):Potassium t-butoxide (15.74 g, 140 mmol) in DMF (50 mL) was added to a solution of 2- fluoro-l-methoxy-4-nitrobenzene (12 g, 70.1 mmol) and 2-(4-chlorophenoxy)acetonitrile (11.75 g, 70.1 mmol) in DMF (100 mL) at -20 C. The reaction mixture was stirred for 1 h and then quenched with water. The aqueous layer was extracted with ethyl acetate. Organic layer was separated, washed with brine, dried over sodium sulphate, filtered and concentrated in vacuo. The crude product was purified by flash chromatography using 3%> ethyl acetate in hexane to afford title compound (3.6 g, 23.21%) as a solid. 1H NMR (400MHz, CDCI3): delta 8.05 (d, J = 10.84 Hz, 1H), 7.27-7.23 (m, 1H), 4.28 (s, 2H), 4.05 (s, 3H); ESI-MS m/z = 209 (M-H)"; LCMS Purity: 95%
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