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With sodium acetate In N,N-dimethyl-formamide at 100℃; for 16 h;
Step 1c. 5-Nitrobenzofuran (Compound 104) A mixture of compound 103 (7.30 g, 30.8 mmol), sodium acetate (10.1 g, 123 mmol) and N,N-dimethylformamide (70 mL) was stirred and heated to 100° C. for 16 hours. The precipitate was filtered and washed with N,N-dimethylformamide. The combined filtrate was evaporated to leave a residue which was purified through a short silica gel column (eluant: ethyl acetate/petroleum ether=1/10) to provide the title compound 104 as a brown solid (3.0 g, 60percent).
With triethylamine; triphenylphosphine;palladium dichloride; at 100℃; for 16h;
Step 1b. ((2-Fluoro-5-nitrophenyl)ethynyl)trimethylsilane (Compound 103) A mixture of compound 102 (2.5 g, 11.4 mmol), triphenylphosphine (0.114 g, 0.44 mmol), palladium (II) chloride (0.045 g, 0.26 mmol) and triethylamine (28 ml) was stirred and heated to 100 C. under nitrogen for 16 hours. The mixture was cooled to room temperature and the precipitate was filtered. The solid was washed with triethylamine and the combined filtrate was evaporated to leave a dark brown oil which was distilled out at 120 C. under reduced pressure to gave compound 103 as a brown yellow solid (1.708 g, 63%): LCMS: 238 [M+1]+.
40%
With triphenylphosphine;palladium diacetate; In triethylamine; at 100℃;
A mixture of compound 0602 (11.Og, 50 mmol) , ethynyltrimethylsilane (7.5 g, 75 mmol), triphenylphosphine (0.5 g) and palladium (II) acetate (0.25 g) in 125 mL of deaerated triethylamine was heated at 100 0C overnight under argon. The reaction was cooled and was filtrated, and the filtrate was concentrated to a dark brown oil which was distilled under reduce pressure to give title compound 0603 as a light brown solid (4.7 g, 40%). 1H NMR (CDCl3): delta 0.3 (s, 9H, SiCH), 7.22 (t, J= 9.0 Hz, IH), 8.2-8.5 (m, 2H).
40%
palladium diacetate; triphenylphosphine; In triethylamine; at 100℃;
Step 31b. ((2-Fluoro-5-nitrophenyl)ethynyl)trimethylsilane (Compound 0603) A mixture of compound 0602 (11.0 g, 50 mmol), ethynyltrimethylsilane (7.5 g, 75 mmol), triphenylphosphine (0.5 g) and palladium (II) acetate (0.25 g) in 125 mL of deaerated triethylamine was heated at 100 C. overnight under argon. The reaction was cooled and was filtrated, and the filtrate was concentrated to a dark brown oil which was distilled under reduce pressure to give title compound 0603 as a light brown solid (4.7 g, 40%). 1H NMR (CDCl3): delta 0.3 (s, 9H, SiCH), 7.22 (t, J=9.0 Hz, 1H), 8.2-8.5 (m, 2H).
40%
With triethylamine;palladium diacetate; triphenylphosphine; at 100℃;
Step 31b. ((2-Fluoro-5-nitrophenyl)ethynyl) trimethylsilane (Compound 0603); A mixture of compound 0602 (11.0 g, 50 mmol), ethynyltrimethylsilane (7.5 g, 75 mmol), triphenylphosphine (0.5 g) and palladium (II) acetate (0.25 g) in 125 mL of deaerated triethylamine was heated at 100 C. overnight under argon. The reaction was cooled and was filtrated, and the filtrate was concentrated to a dark brown oil which was distilled under reduce pressure to give title compound 0603 as a light brown solid (4.7 g, 40%). 1H NMR (CDCl3): delta 0.3 (s, 9H, SiCH), 7.22 (t, J=9.0 Hz, 1H), 8.2-8.5 (m, 2H).
With diisopropylamine;copper(l) iodide; bis(benzonitrile)palladium(II) dichloride; tri-tert-butyl phosphine; In tetrahydrofuran; at 20℃; for 5h;
A mixture of bis (benzonitril) dichloropalladium (II) (53 mg, 0.14 mmol) and copper (I) iodide (26 mg, 0.14 mmol) in 6 mL dry THF was purged with argon for 3 minutes, then was added tri (tert-butyl phosphine) (69 ul, 0.28 mmol), TMS acetylene (0.77 ml, 5.5 mmol), <strong>[701-45-1]3-bromo-4-fluoronitrobenzene</strong> 505 mg, 2.295 mmol), and di-isopropylamine (0.77 ml, 5.5 mmol). The mixture was stirred at room temperature for 5 hours under argon. To the reaction mixture was added 7 mL 1 M TBAF/THF and the mixture was stirred at room temperature for 10 minutes. Workup and purification by column chromatography (silica, 5% - 35% EtOAc/hexane) give 2-ethynyl-1-fluoro-4-nitro-benzene.
4600 mg
With palladium diacetate; triethylamine; triphenylphosphine; at 10℃; for 4.5h;Inert atmosphere;
1.126 ml of ethynyl(trimethyl)silane, 55 mg of triphenylphosphine and 24 mg of palladium (2+) acetate are added to a solution of 1.169 g of <strong>[701-45-1]2-bromo-1-fluoro-4-nitrobenzene</strong> in 13 ml of triethylamine with stirring and under argon. After four and a half hours at a temperature of 100 C., the reaction medium is cooled and the insoluble material is filtered off through sintered glass. The filtrate is concentrated to dryness under reduced pressure. After two silica column purifications, eluent: 90/10 heptane/EtOAc then 955 heptane/EtOAc, 460 mg of [(2-fluoro-5-nitrophenyl)ethynyl](trimethyl)silane are obtained in the form of a yellow solid,
With tetrabutyl ammonium fluoride; In tetrahydrofuran; at 20.0℃; for 0.166667h;
A mixture of bis (benzonitril) dichloropalladium (II) (53 mg, 0.14 mmol) and copper (I) iodide (26 mg, 0.14 mmol) in 6 mL dry THF was purged with argon for 3 minutes, then was added tri (tert-butyl phosphine) (69 ul, 0.28 mmol), TMS acetylene (0.77 ml, 5.5 mmol), 3-bromo-4-fluoronitrobenzene 505 mg, 2.295 mmol), and di-isopropylamine (0.77 ml, 5.5 mmol). The mixture was stirred at room temperature for 5 hours under argon. To the reaction mixture was added 7 mL 1 M TBAF/THF and the mixture was stirred at room temperature for 10 minutes. Workup and purification by column chromatography (silica, 5% - 35% EtOAc/hexane) give 2-ethynyl-1-fluoro-4-nitro-benzene.
With sodium acetate; In N,N-dimethyl-formamide; at 100℃; for 16h;
Step 1c. 5-Nitrobenzofuran (Compound 104) A mixture of compound 103 (7.30 g, 30.8 mmol), sodium acetate (10.1 g, 123 mmol) and N,N-dimethylformamide (70 mL) was stirred and heated to 100 C. for 16 hours. The precipitate was filtered and washed with N,N-dimethylformamide. The combined filtrate was evaporated to leave a residue which was purified through a short silica gel column (eluant: ethyl acetate/petroleum ether=1/10) to provide the title compound 104 as a brown solid (3.0 g, 60%).