3-Fluoro-4-nitroanisole

To a solution of 3-fluoro-4-nitro-phenol (25.3 g, 0.16 mol) in acetone (160 ml), potassium carbonate (41.7 g, 0.30 mol) and methyl iodide (20.0 ml, 0.32 mol) are added at ambient temperature. The reaction mixture is stirred at 40 C for 3 h. After cooling down to room temperature, dichloromethane is added to the reaction mixture, which is filtrated and evaporated. Dichloromethane is added to the residue and the organic phase is washed with H2O and brine, dried over sodium sulfate and evaporated down to give 2-fluoro-4-methoxy-1-nitro-benzene in 98 percent yield. Rf=0.5 (n-hexane:ethyl acetate = 10:1). 1H-NMR (400MHz, CDCl3) δ: 3.90 (s, 3H), 6.72-6.79 (m, 2H), 8.06-8.13 (m, 1H)4-Methoxy-2-fluoro-1-nitrobenzene Potassium carbonate (79.0 g, 0.57 mol) was added to a stirred solution of 3-fluoro-4- nitrophenol (45.0 g, 0.29 mol) and methyl iodide (50.0 mL, 0.81 mol) in methylethyl ketone (450 mL) at room temperature. The suspension was stirred at 40 A solution of 3-fluoro-4-nitrophenol (75 g, 0.48 mol) in acetone (700 mL) was cooled in an ice-water bath. 1, 8-Diazabicyclo [5, 4, [0]] undec-7-ene (145 g, 0.96 mol) was then added over ca. 5 min. Finally, [IODOMETHANE] (135 g, 0.96 mol) was added over 10 min. The mixture was stirred at room temperature for 16 hr. Additional 1, 8-diazabicyclo [5, 4, [0]] undec-7-ene (73 g, 0.48 mol) and iodomethane (68 g, 0.48 mol) were added, and the mixture was warmed to 50 [C] for 1 hr. After a solid was removed by filtration, the concentrated filtrate was mixed with ethyl acetate and 1 M hydrochloric acid. The organic layer was washed with additional hydrochloric acid and aqueous sodium bicarbonate, concentrated, and stirred in 1percent ethyl acetate in hexanes. The resulting solid was collected and dried to give 72 g (88percent) of the title compound.A solution of 3-fluoro-4-nitrophenol (75 g, 0.48 mol) in acetone (700 mL) was cooled in an ice-water bath. 1, 8-Diazabicyclo[5, 4, 0]undec-7-ene (145 g, 0.96 mol) was then added over ca. 5 min. [0157] A solution of 3-fluoro-4-nitrophenol (75 g, 0.48 mol) in acetone (700 mL) was cooled in an ice-water bath. 1, 8-Diazabicyclo[5, 4, 0]undec-7-ene (145 g, 0.96 mol) was then added over ca. 5 min. Finally, iodomethane (135 g, 0.96 mol) was added over 10 min. The mixture was stirred at room temperature for 16 hr. Additional 1, 8-diazabicyclo[5, 4, 0]undec-7-ene (73 g, 0.48 mol) and iodomethane (68 g, 0.48 mol) were added, and the mixture was warmed to 50° C. for 1 hr. After a solid was removed by filtration, the concentrated filtrate was mixed with ethyl acetate and 1 M hydrochloric acid. The organic layer was washed with additional hydrochloric acid and aqueous sodium bicarbonate, concentrated, and stirred in 1percent ethyl acetate in hexanes. The resulting solid was collected and dried to give 72 g (88percent) of the title compound.[0303j Step A: Preparation of 2-fluoro-4-methoxy- 1 -nitrobenzene: To a suspension of 3-fluoro-4-nitrophenol (0.16 g, 1 mmol) and potassium carbonate (0.42 g, 3 mmol) in DMF (10 mL) was added iodomethane (0.24 g, 2.0 mmol) at 0 °C. The reaction was stirred at 0 °C for 1 hour and water (50 mL) was added. The solid formed was collected by filtration, washed with water and dried to give 2-fluoro-4-methoxy-1-nitrobenzene (0.15 g, 88percent) as solid.2-Fluoro-4-methoxy-l-nitro-benzeneK2-Fluoro-4-methoxy-1-nitro-benzene Step 5a. To a stirred solution of 3-fluoro-4-nitrophenol (5 g, 31.8 mmol) in acetone (100 mL) at room temperature was added potassium carbonate (15.4O g, 111 mmol) in one portion followed by dimethyl sulphate (6.04 mL, 63.7 mmol) dropwise. The resulting yellow suspension was stirred at reflux for 2 h. The reaction mixture was then cooled to room temperature, filtered and the filtrate was evaporated. The resulting yellow liquid was Preparation 7; Preparation of 4-ethenyl-3, 8-difluoro-6-(methoxy)quinoline; a) 3-fluoro-4-nitrophenyl methyl ether; A solution of 3-fluoro-4-nitrophenol (25 g, 0.159 mmol) in acetonitrile (500 mL) and methanol (500 mL) was treated with diisopropyl ethylamine (28 mL). The reaction mixture was cooled in an ice-bath and after 30 minutes, trimethylsilyldiazomethane was added dropwise. The mixture was stirred at room temperature for 18 hours then evaporated under vacuum to afford the product as an oil (29.4 g, 100percent). MS (+ve ion electrospray) m/z 172 (MH+).

Molecular Weight:171.13
XLogP3:1.9
Hydrogen Bond Acceptor Count:4
Rotatable Bond Count:1
Exact Mass:171.03317122
Monoisotopic Mass:171.03317122
Topological Polar Surface Area:55
Heavy Atom Count:12
Complexity:171
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes