1-(4-fluoro-2-hydroxyphenyl)ethanone

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A 1.0 M tetrahydrofuran solution of lithium bis(trimethylsilyl)amide (39.0 mL, 39.0 mmol) was stirred at −78° C. and treated over a 25 min period with a solution of 1-(4-fluoro-2-hydroxyphenyl)ethanone (2.00 g, 13.0 mmol) in 50 mL of tetrahydrofuran. The resulting solution was stirred at −78° C. for 1 h, and then at −15° C. for 2 h. After being cooled again to −78° C., the solution was treated with a solution of dimethyl carbonate (1.20 mL, 14.3 mmol) in tetrahydrofuran (5 mL). The resulting mixture was allowed to warm to rt where it stirred overnight. After this time, the mixture was poured over ice and then concentrated hydrochloric acid (10 mL) was added. The resulting mixture was extracted three times with dichloromethane. The combined organic phases were washed twice with water, dried over sodium sulfate and then concentrated under vacuum to yield a residue. The residue was purified by radial thin-layer chromatography (silica gel, 2-40% ethyl acetate-hexane) to provide methyl 3-(4-fluoro-2-hydroxyphenyl)-3-oxopropanoate as a white solid (1.76 g, 64%). 1H NMR (400 MHz, CDCl3) δ ppm 3.78 (s, 3 H) 3.98 (s, 2 H) 6.62-6.71 (m, 2 H) 7.69 (dd, J=8.9, 6.4 Hz, 1 H) 12.15 (d, J=1.5 Hz, 1 H). Mass spectrum m/z 213.14 (M+H)+. at −15° C. for 2 h After being cooled again to −78° C. to warm to rt where it stirred overnight After this time, the mixture was poured over ice The resulting mixture was extracted three times with dichloromethane The combined organic phases were washed twice with water dried over sodium sulfate concentrated under vacuum to yield a residue The residue was purified by radial thin-layer chromatography (silica gel, 2-40% ethyl acetate-hexane)

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of 4'-fluoro-2'-hydroxyacetophenone, oxime (47.0 g, 0.278 mol) in tetrahydrofuran is heated to just under reflux, treated with a solution of 1,1'-carbonyldiimidazole (55.0 g, 0.340 mol) and triethylamine (39.0 g, 0.390 mol) in tetrahydrofuran, refluxed for one hour, cooled, concentrated in vacuo, and poured into an ice-water mixture. The resultant aqueous mixture is extracted with ether. The organic extracts are combined, washed sequentially with saturated ammonium chloride solution and brine, dried over anhydrous magnesium sulfate, and concentrated in vacuo to obtain an oil. Column chromatography of the oil using silica gel and a methylene chloride/hexanes solution (1:1) gives the title product as a yellow oil which is identified by 1H NMR spectral analysis. is heated to just under reflux refluxed for one hour cooled concentrated in vacuo poured into an ice-water mixture The resultant aqueous mixture is extracted with ether washed sequentially with saturated ammonium chloride solution and brine dried over anhydrous magnesium sulfate concentrated in vacuo to obtain an oil

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of 4′-fluoro-2′-hydroxyacetophenone, oxime (47.0 g, 0.278 mol) in tetrahydrofuran is heated to just under reflux, treated with a solution of 1,1′-carbonyldiimidazole (55.0 g, 0.340 mol) and triethylamine (39.0 g, 0.390 mol) in tetrahydrofuran, refluxed for one hour, cooled, concentrated in vacuo, and poured into an ice-water mixture. The resultant aqueous mixture is extracted with ether. The organic extracts are combined, washed sequentially with saturated ammonium chloride solution and brine, dried over anhydrous magnesium sulfate, and concentrated in vacuo to obtain an oil. Column chromatography of the oil using silica gel and a methylene chloride/hexanes solution (1:1) gives the title product as a yellow oil which is identified by 1H NMR spectral analysis. is heated to just under reflux refluxed for one hour cooled concentrated in vacuo poured into an ice-water mixture The resultant aqueous mixture is extracted with ether washed sequentially with saturated ammonium chloride solution and brine dried over anhydrous magnesium sulfate concentrated in vacuo to obtain an oil

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of 4′-fluoro-2′-hydroxyacetophenone, oxime (47.0 g, 0.278 mol) in tetrahydrofuran is heated to just under reflux, treated with a solution of 1,1′-carbonyldiimidazole (55.0 g, 0.340 mol) and triethylamine (39.0 g, 0.390 mol) in tetrahydrofuran, refluxed for one hour, cooled, concentrated in vacuo, and poured into an ice-water mixture. The resultant aqueous mixture is extracted with ether. The organic extracts are combined, washed sequentially with saturated ammonium chloride solution and brine, dried over anhydrous magnesium sulfate, and concentrated in vacuo to obtain an oil. Column chromatography of the oil using silica gel and a methylene chloride/hexanes solution (1:1) gives the title product as a yellow oil which is identified by 1H NMR spectral analysis. is heated to just under reflux refluxed for one hour cooled concentrated in vacuo poured into an ice-water mixture The resultant aqueous mixture is extracted with ether washed sequentially with saturated ammonium chloride solution and brine dried over anhydrous magnesium sulfate concentrated in vacuo to obtain an oil

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a mixture of (2-hydroxy-4-fluoro phenyl)-1-ethanone (3 g, 19.7 mmol) obtained in Preparation 5, and 4-fluorobenzaldehyde (4.37 g, 19.7 mmol) in methanol was slowly added sodium hydroxide solution at 0° C., under N2 atm. The reaction mixture was allowed to stir for 10 hours at 0-10° C. Water (100 mL) was added to it followed by 6 N HCl (15 mL). Solid separated was filtered off and dried under vacuum to afford 3 g (41%) of the title compound as a yellow solid.

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a mixture of (2-hydroxy-4-fluoro phenyl)-1-ethanone (3 g, 19.7 mmol) obtained in Preparation 5, and 4-fluorobenzaldehyde (4.37 g, 19.7 mmol) in methanol was slowly added sodium hydroxide solution at 0° C., under N2 atm. The reaction mixture was allowed to stir for 10 hours at 0-10° C. Water (100 mL) was added to it followed by 6 N HCl (15 mL). Solid separated was filtered off and dried under vacuum to afford 3 g (41%) of the title compound as a yellow solid.