4-fluoro-2-prop-2-enylphenol

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:; See reaction.notes.procedure_details.

実験手順: To a stirred and refluxing mixture of 162 parts of 2-allyl-4-fluorophenol, 363 parts of 1,3-dibromopropane in 700 parts of water is added dropwise a solution of 56 parts of sodium hydroxide in 175 parts of water. Upon completion, the whole is stirred and refluxed for 8 hours. After cooling, the aqueous layer is separated and extracted with chloroform. The extract is dried over magnesium sulfate, filtered and evaporated. The oily residue is distilled twice, yielding 142 parts of 3-allyl-4-(3-bromopropoxy)fluorobenzene; bp. 160° -170° C. at 14 mm. pressure. refluxing Upon completion, the whole is stirred refluxed for 8 hours After cooling the aqueous layer is separated extracted with chloroform The extract is dried over magnesium sulfate filtered evaporated The oily residue is distilled twice

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

実験手順: 381.8 parts of oily 4-allyloxy-fluorobenzene are heated in an oil-bath for 8 hours at a temperature of about 245° -250° C. After cooling, the reaction mixture is poured onto 1200 parts of hexane. The mixture is extracted three times with sodium hydroxide solution 20% (total volume of sodium hydroxide: 2000 parts). The aqueous layer is washed with petroleum ether, acidified with 1300 parts of concentrated hydrochloric acid solution and extracted with ether. The extract is dried over calcium chloride, filtered and evaporated. The oily residue is distilled in vacuo, yielding 313.6 parts of 2-allyl-4-fluorophenol; bp 143° C at 48 mm. pressure; nD20 : 1.5225; d2020 : 1.1130. After cooling The mixture is extracted three times with sodium hydroxide solution 20% (total volume of sodium hydroxide: 2000 parts) The aqueous layer is washed with petroleum ether extracted with ether The extract is dried over calcium chloride filtered evaporated The oily residue is distilled in vacuo

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

実験手順: To crude (4p), acetic anhydride (36.5 mL, 386.4 mmol) and pyridine (37.5 mL, 463.7 mmol) were added. The resulting mixture was stirred at room temperature for 18 hours, checked by HPLC the next day (reaction appeared mostly complete). The mixture was then poured onto cold H2O/Et2O, the aqueous layer was extracted with Et2O (2×), the combined organic layers were washed sequentially with 10% HCl (3×), saturated NaHCO3 (2×), H2O (2×) and brine, and then dried over anhydrous Na2SO4. After concentration, crude product purity was checked by thin-layer chromatography (hexane/ethyl acetate, 7:3) and HPLC. No mass ion was observed. The crude product (5p) was carried on to next step directly without subsequent purification. reaction the aqueous layer was extracted with Et2O (2×) the combined organic layers were washed sequentially with 10% HCl (3×), saturated NaHCO3 (2×), H2O (2×) and brine dried over anhydrous Na2SO4 After concentration, crude product purity The crude product (5p) was carried on to next step directly without subsequent purification

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To an ice cold solution of 2-allyl-4-fluorophenol (853) (6.0 g, 36.2 mmol) in CHCl3 (180.0 mL) was added slowly the suspension of 77% 3-chloroperoxybenzoic acid (8.1 g, 36.2 mmol) in CHCl3 (36.2 mL). The resulting mixture was stirred at 0° C. for 2 hours, then washed with NaHCO3 (100 mL), water (2×100 mL), brine (100 mL) and dried over sodium sulfate, filtered and concentrated in vacuo. The residue was purified by flash chromatography on silica gel (30-40% EtOAc in hexanes) to provide the desired product (5-fluoro-2,3-dihydrobenzofuran-2-yl)methanol (854) (3.8 g, 57.7%) as a yellow oil. washed with NaHCO3 (100 mL), water (2×100 mL), brine (100 mL) dried over sodium sulfate filtered concentrated in vacuo The residue was purified by flash chromatography on silica gel (30-40% EtOAc in hexanes)

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

実験手順: A mixture of 1.5 g of 2-allyl-4-fluorophenol, 3.1 g of 8-(3-chloropropyl)-1-phenyl-4-oxo-1,3,8-triazaspiro[4,5]decane, 0.7 g of potassium carbonate and 40 ml of toluene was heated under reflux for 10 hours. After cooling, the reaction mixture was washed with water, dried over sodium sulfate and evaporated under reduced pressure. The residue was triturated with ether, cooled and filtered to give 8-{3-(2-allyl-4-fluorophenoxy)propyl}-1-phenyl-4-oxo-1,3,8-triazaspiro[4,5]decane, m.p. 110° - 113° C; recrystallized from cyclohexane, m.p. 117° - 117.5° C. was heated under reflux for 10 hours After cooling the reaction mixture was washed with water dried over sodium sulfate evaporated under reduced pressure The residue was triturated with ether cooled filtered

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

実験手順: To a stirred and refluxing mixture of 162 parts of 2-allyl-4-fluorophenol, 363 parts of 1,3-dibromopropane in 700 parts of water is added dropwise a solution of 56 parts of sodium hydroxide in 175 parts of water. Upon completion, the whole is stirred and refluxed for 8 hours. After cooling, the aqueous layer is separated and extracted with chloroform. The extract is dried over magnesium sulfate, filtered and evaporated. The oily residue is distilled twice, yielding 142 parts of 3-allyl-4-(3-bromopropoxy)fluorobenzene; bp. 160° -170° C. at 14 mm. pressure. refluxing Upon completion, the whole is stirred refluxed for 8 hours After cooling the aqueous layer is separated extracted with chloroform The extract is dried over magnesium sulfate filtered evaporated The oily residue is distilled twice

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

実験手順: To a stirred and refluxing mixture of 162 parts of 2-allyl-4-fluorophenol, 363 parts of 1,3-dibromopropane in 700 parts of water is added dropwise a solution of 56 parts of sodium hydroxide in 175 parts of water. Upon completion, the whole is stirred and refluxed for 8 hours. After cooling, the aqueous layer is separated and extracted with chloroform. The extract is dried over magnesium sulfate, filtered and evaporated. The oily residue is distilled twice, yielding 142 parts of 3-allyl-4-(3-bromopropoxy)fluorobenzene; bp. 160° -170° C. at 14 mm. pressure. refluxing Upon completion, the whole is stirred refluxed for 8 hours After cooling the aqueous layer is separated extracted with chloroform The extract is dried over magnesium sulfate filtered evaporated The oily residue is distilled twice

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

実験手順: 381.8 parts of oily 4-allyloxy-fluorobenzene are heated in an oil-bath for 8 hours at a temperature of about 245° -250° C. After cooling, the reaction mixture is poured onto 1200 parts of hexane. The mixture is extracted three times with sodium hydroxide solution 20% (total volume of sodium hydroxide: 2000 parts). The aqueous layer is washed with petroleum ether, acidified with 1300 parts of concentrated hydrochloric acid solution and extracted with ether. The extract is dried over calcium chloride, filtered and evaporated. The oily residue is distilled in vacuo, yielding 313.6 parts of 2-allyl-4-fluorophenol; bp 143° C at 48 mm. pressure; nD20 : 1.5225; d2020 : 1.1130. After cooling The mixture is extracted three times with sodium hydroxide solution 20% (total volume of sodium hydroxide: 2000 parts) The aqueous layer is washed with petroleum ether extracted with ether The extract is dried over calcium chloride filtered evaporated The oily residue is distilled in vacuo

反応条件: temp:0.00; pressure:0.00; stir:

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

実験手順: To crude (4p), acetic anhydride (36.5 mL, 386.4 mmol) and pyridine (37.5 mL, 463.7 mmol) were added. The resulting mixture was stirred at room temperature for 18 hours, checked by HPLC the next day (reaction appeared mostly complete). The mixture was then poured onto cold H2O/Et2O, the aqueous layer was extracted with Et2O (2×), the combined organic layers were washed sequentially with 10% HCl (3×), saturated NaHCO3 (2×), H2O (2×) and brine, and then dried over anhydrous Na2SO4. After concentration, crude product purity was checked by thin-layer chromatography (hexane/ethyl acetate, 7:3) and HPLC. No mass ion was observed. The crude product (5p) was carried on to next step directly without subsequent purification. 1HNMR (400 MHz, CDCl3) δ 7.04-6.91 (m, 3H), 6.09-5.65 (m, 1H), 5.19-5.06 (m, 2H), 3.27 (d, J=6.26 Hz, 2H), 2.30 (s, CH3). reaction the aqueous layer was extracted with Et2O (2×) the combined organic layers were washed sequentially with 10% HCl (3×), saturated NaHCO3 (2×), H2O (2×) and brine dried over anhydrous Na2SO4 After concentration, crude product purity The crude product (5p) was carried on to next step directly without subsequent purification