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With sodium hydride In tetrahydrofuran for 4h; Heating; |
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With potassium carbonate In acetonitrile |
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With potassium carbonate In acetone at 20℃; for 2 - 16h; Heating / reflux; |
A.A; 1
2'-Hydroxyacetophenone (10.0 g, 73.5 mmol) is treated with ethyl bromoacetate(11.4 mL, 0.103 mol, d 1.506) and K2CO3 (40.5 g, 0.294 mol) in accordance with Method A to afford the title compound (20.7 g) as a white wax which is used as is without further purification: LC/MS tR 1.82 min; MS (ES+) m/z 223 (M+H), 245 (M+Na); 1H NMR (360 MHz, CDCl3, δH) 7.76 (IH, dd), 7.44 (IH, ddd), 7.05 (IH, app td), 6.83 (IH, dd), 4.72 (2H, s), 4.28 (2H, q), 2.72 (3H, s), 1.30 (3H, t).; Method A[0206] In accordance with the procedure of Nielek and Lesiak (Chem. Ber., 1982, 115,1247-1251), a suspension of the phenol (1 equiv) and K2CO3 (2-4 equiv) in acetone (5 vol) stirring at rt is treated with the α-haloacetate (1.2-1.4 equiv) then heated at reflux for 2-16 h. Reaction progress is monitored by LC/MS. On completion, the reaction mixture is allowed to cool to rt then filtered. The filter cake is washed with EtOAc (10 vol) and the filtrate is coned in vacuo to afford the desired product. |
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With potassium carbonate In acetone for 60h; Reflux; |
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With potassium carbonate In acetone for 60h; Inert atmosphere; Reflux; |
4.2.13. 3-Methylbenzofuran (7)
Following the procedure of Nielek and Lesiak,24 2-hydroxyacetophenone (1.20 mL, 10.0 mmol), ethylbromoacetate (1.55 mL, 14.0 mmol) and K2CO3 (5.53 g, 40.0 mmol) were suspended in dry acetone (10 mL) and the mixture was refluxed for 60 h. On completion, the reaction mixture was cooled to rt and filtered. The filter cake was washed with EtOAc and the filtrate was concentrated under reduced pressure to afford the desired product. The crude product was used without further purification. To a solution of the obtained ethyl ester (1 equiv) in EtOH (4 mL) was added NaOH (3 N, 6 mL) and the resulting mixture was stirred for 2 h. Reaction progress was monitored by TLC. On completion, EtOH was removed in vacuo, the residual aqueous mixture was cooled to 0 °C and treated with conc. HCl until pH 1-2. The resulting precipitate was collected by filtration and washed with water to afford on drying the desired product. The crude product was used without further purification. A suspension of the carboxylic acid (472 mg, 2.40 mmol) and NaOAc (1.20 g, 14.6 mmol) in Ac2O (1.37 mL, 14.6 mmol) was warmed to reflux and stirred for 18 h. On completion, the reaction mixture was cooled to rt and poured onto ice. The aqueous suspension was extracted with Et2O (3×) and the combined organic phases dried over anhydrous MgSO4. After removal of the solvent under reduced pressure, the compound was purified by column chromatography (pentane) yielding 3-methylbenzofurane (7) (225 mg, 1.70 mmol, 17% over 3 steps) as a colourless, volatile liquid. |
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With potassium carbonate In N,N-dimethyl-formamide at 20℃; for 16h; |
6.1 Step 1: Synthesis of 2-(2'-acetylphenoxy)acetic acid(E-2)
Compound E-1 2'-hydroxyacetophenone (20 g, 146.9 mmol)Carbonic acid (32.5 g, 235 mmol) was added to DMF (120 mL), and the mixture was stirred and stirred at room temperature, and ethyl bromoacetate (29.4 g, 176.3 mmol) was slowly added dropwise, and the mixture was reacted at room temperature for 16 hours. 50 mL of water was added to the reaction to precipitate a large amount of solid. After stirring at room temperature for 30 minutes, the solid was filtered, and the filter cake was washed with water several times.The filtered solid is dried under reduced pressure to obtainCrude ethyl 2-(2'-acetylphenol)acetate. The crude product was dissolved in tetrahydrofuran solution (100 mL), 4M aqueous sodium hydroxide solution (50 mL) was added, and the mixture was stirred at room temperature for 1 hour, and concentrated under reduced pressure to remove most solvent. The residue was adjusted to pH with acid. Filter, wash the filter cake several times with water until the filtrate is neutral. The filtered solid was dried under reduced pressure to give the product 26.2 g, yield 80% |
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With potassium carbonate In N,N-dimethyl-formamide at 20℃; for 16h; Inert atmosphere; |
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With potassium carbonate In acetone |
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With potassium carbonate In acetonitrile at 65℃; for 18h; |
Asolution of o-hydroxyphenyl ketone (17,2.72 g, 20.0 mmol), ethyl bromoacetate 18 (3.984 g, 24.0 mmol) and K2CO3 (5520 mg, 40.0mmol) in MeCN (80 mL) was heated to 65°C for 18 hours. The insoluble solid wasfiltered off, washed with ethyl acetate. The filtrate was concentrated underreduced pressure. The residue was diluted with water (100 mL), extracted withdiethyl ether (3 × 50 mL), and the combined organic layers were washed withbrine, dried over sodium sulfate, filtered and the solvent was evaporated undervacuum to give crude product 19 (3.3g, 75%). Crude product was used in the next step without further purification. |
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With potassium carbonate In acetone Inert atmosphere; Reflux; |
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