ethyl cyclopent-3-ene-1-carboxylate

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

実験手順: A solution containing 84.6 g of N-methylmorpholine N-oxide, 1 g of osmium tetroxide, 230 ml of water and 115 ml of acetone was allowed to stir for 30 minutes at room temperature. To this stirred mixture was added very slowly over at least 8 hours, a solution of 80 g of ethyl 3-cyclopentene-1-carboxylate in 115 ml of acetone. The stirred mixture was heated at 50° C. for 2 hours to complete the reaction (verified by TLC examination using ethyl acetate/hexane 70/30). Sodium bisulfite (~10 g) was added, the stirring continued for a further 15 minutes, and the mixture filtered through Celite. The pH of the filtrate was adjusted to 7 by the addition of 12 N sulfuric acid (37 ml), the acetone evaporated, the pH of the residual solution adjusted to 2 with 12 N sulfuric acid (13 ml) and the solution extracted with ethyl acetate (4×250 ml). Evaporation of the dried ethyl acetate solution gave 4-ethoxycarbonyl-1,2-cyclopentanediol. To this stirred mixture was added very slowly over at least 8 hours The stirred mixture was heated at 50° C. for 2 hours the stirring continued for a further 15 minutes the mixture filtered through Celite The pH of the filtrate was adjusted to 7 by the addition of 12 N sulfuric acid (37 ml) the acetone evaporated the solution extracted with ethyl acetate (4×250 ml) Evaporation of the dried ethyl acetate solution

反応条件: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A flame-dried 500 mL flask was charged with 2,6-dibromophenol (1.20 g, 4.76 mmol), tungsten oxychloride (0.813 g, 2.38 mmol), and anhydrous toluene (25 mL). The resulting suspension was heated at reflux under nitrogen for 1 h, and then the solvent was evaporated in vacuo. The solid residue was broken up with a spatula and dried in vacuo for 30 min. To the residue were added toluene (160 mL), Et4Pb (1.54 g, 4.76 mL), and 702 (22 g, 131.0 mmol). The mixture was heated at 90° C. under nitrogen for 1.5 h. After being cooled to r.t., the mixture was filtered through a celite, and the celite was rinsed with t-BuOMe. The combined filtrates were washed with 1% NaOH soln, water, and brine, and concentrated by evaporation at reduced pressure. The residue was distilled (37-38° C./1 Torr) to give 13.06 g (71%) of 703 as a colorless liquid. 1H NMR (400 MHz, CDCl3) δ 5.67 (s, 2H, CH═CH), 4.14 (q, 2H, J=7.2 Hz, OCH2), 3.11 (pentuplet, J=7.6 Hz, 1H, CH), 2.65 (d, J=7.6 Hz, 4H, 2 CH2), 1.27 (t, J=7.2 Hz, 3 H, CH3). The resulting suspension was heated at reflux under nitrogen for 1 h the solvent was evaporated in vacuo dried in vacuo for 30 min After being cooled to r.t. the mixture was filtered through a celite the celite was rinsed with t-BuOMe The combined filtrates were washed with 1% NaOH soln water, and brine, and concentrated by evaporation at reduced pressure The residue was distilled (37-38° C./1 Torr)

反応条件: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A flame-dried 500 mL flask was charged with 2,6-dibromophenol (1.20 g, 4.76 mmol), tungsten oxychloride (0.813 g, 2.38 mmol), and anhydrous toluene (25 mL). The resulting suspension was heated at reflux under nitrogen for 1 h, and then the solvent was evaporated in vacuo. The solid residue was broken up with a spatula and dried in vacuo for 30 min. To the residue were added toluene (160 mL), Et4Pb (1.54 g, 4.76 mL), and 702 (22 g, 131.0 mmol). The mixture was heated at 90° C. under nitrogen for 1.5 h. After being cooled to r.t., the mixture was filtered through a celite, and the celite was rinsed with t-BuOMe. The combined filtrates were washed with 1% NaOH soln, water, and brine, and concentrated by evaporation at reduced pressure. The residue was distilled (37-38° C./1 Torr) to give 13-06 g (71%) of 703 as a colorless liquid. 1H NMR (400 MHz, CDCl3) δ 5.67 (s, 2H, CH═CH), 4.14 (q, 2H, J=7.2 Hz, OCH2), 3.11 (pentuplet, J=7.6 Hz, 1H, CH), 2.65 (d, J=7.6 Hz, 4H, 2 CH2), 1.27 (t, J=7.2 Hz, 3H, CH3). The resulting suspension was heated at reflux under nitrogen for 1 h the solvent was evaporated in vacuo dried in vacuo for 30 min After being cooled to r.t. the mixture was filtered through a celite the celite was rinsed with t-BuOMe The combined filtrates were washed with 1% NaOH soln water, and brine, and concentrated by evaporation at reduced pressure The residue was distilled (37-38° C./1 Torr)

反応条件: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A flame-dried 500 mL flask was charged with 2,6-dibromophenol (1.20 g, 4.76 mmol), tungsten oxychloride (0.813 g, 2.38 mmol), and anhydrous toluene (25 mL). The resulting suspension was heated at reflux under nitrogen for 1 h, and then the solvent was evaporated in vacuo. The solid residue was broken up with a spatula and dried in vacuo for 30 min. To the residue were added toluene (160 mL), Et4Pb (1.54 g, 4.76 mL), and 702 (22 g, 131.0 mmol). The mixture was heated at 90° C. under nitrogen for 1.5 h. After being cooled to r.t., the mixture was filtered through a celite, and the celite was rinsed with t-BuOMe. The combined filtrates were washed with 1% NaOH soln, water, and brine, and concentrated by evaporation at reduced pressure. The residue was distilled (37-38° C./1 Torr) to give 13.06 g (71%) of 703 as a colorless liquid. 1H NMR (400 MHz, CDCl3) δ 5.67 (s, 2H, CH═CH), 4.14 (q, 2H, J=7.2 Hz, OCH2), 3.11 (pentuplet, J=7.6 Hz, 1H, CH), 2.65 (d, J=7.6 Hz, 4H, 2CH2), 1.27 (t, J=7.2 Hz, 3H, CH3). The resulting suspension was heated at reflux under nitrogen for 1 h the solvent was evaporated in vacuo dried in vacuo for 30 min After being cooled to r.t. the mixture was filtered through a celite the celite was rinsed with t-BuOMe The combined filtrates were washed with 1% NaOH soln water, and brine, and concentrated by evaporation at reduced pressure The residue was distilled (37-38° C./1 Torr)

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

実験手順: To a solution of diisopropylamine (10 mL, 72 mmol) in anhydrous THF (50 mL) was added n-butyl lithium (29 mL, 72 mmol, 2.5 M solution in hexane) over 20 min at −78° C. The mixture was stirred at 0° C. under nitrogen for 1 h. The freshly prepared lithium diisopropylamide was added to a mixture of ethyl cyclopent-3-enecarboxylate (6.7 g, 47.9 mmol) in anhydrous THF (50 mL) over 20 minutes at −78° C. After another 1 hour at this temperature, iodoethane (11.2 g, 72 mmol) was added over 20 min. Then the mixture was stirred at room temperature for 2 h and quenched with saturated aqueous ammonium chloride solution. The aqueous layer was extracted with ether (3×100 mL). The combined organic layers were washed with diluted hydrochloric acid (1 N), then washed with brine, dried over anhydrous sodium sulfate and filtered. Concentration gave the titled compound (7 g crude) which was used in the next step without further purification. 1H NMR (400 MHz, CDCl3) δ ppm 5.60 (s, 2H), 4.21-4.12 (m, 2H), 2.92-2.84 (m, 2H), 2.31-2.25 (m, 2H), 1.75-1.67 (m, 2H), 1.29-1.24 (m, 3H), 0.88-0.82 (m, 3H). Then the mixture was stirred at room temperature for 2 h quenched with saturated aqueous ammonium chloride solution The aqueous layer was extracted with ether (3×100 mL) The combined organic layers were washed with diluted hydrochloric acid (1 N) washed with brine dried over anhydrous sodium sulfate filtered Concentration

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

実験手順: To a solution of diisopropylamine (10 mL, 72 mmol) in anhydrous THF (50 mL) was added n-butyl lithium (29 mL, 72 mmol, 2.5 M solution in hexane) over 20 min at −78° C. The mixture was stirred at 0° C. under nitrogen for 1 h. The freshly prepared lithium diisopropylamide was added to a mixture of ethyl cyclopent-3-enecarboxylate (6.7 g, 47.9 mmol) in anhydrous THF (50 mL) over 20 minutes at −78° C. After another 1 hour at this temperature, iodoethane (11.2 g, 72 mmol) was added over 20 min. Then the mixture was stirred at room temperature for 2 h and quenched with saturated aqueous ammonium chloride solution. The aqueous layer was extracted with ether (3×100 mL). The combined organic layers were washed with diluted hydrochloric acid (1 N), then washed with brine, dried over anhydrous sodium sulfate and filtered. Concentration gave the titled compound (7 g crude) which was used in the next step without further purification. 1H NMR (400 MHz, CDCl3) δ ppm 5.60 (s, 2H), 4.21-4.12 (m, 2H), 2.92-2.84 (m, 2H), 2.31-2.25 (m, 2H), 1.75-1.67 (m, 2H), 1.29-1.24 (m, 3H), 0.88-0.82 (m, 3H). Then the mixture was stirred at room temperature for 2 h quenched with saturated aqueous ammonium chloride solution The aqueous layer was extracted with ether (3×100 mL) The combined organic layers were washed with diluted hydrochloric acid (1 N) washed with brine dried over anhydrous sodium sulfate filtered Concentration

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

実験手順: To a stirred solution of cyclopent-3-enecarboxylic acid (10 g, 89.3 mmol) in anhydrous ethanol (30 mL) was added sulfurous dichloride (15.9 g, 134 mmol) at 0° C. The reaction mixture was stirred at room temperature overnight and then concentrated. The residue was poured into water. The resulting mixture was extracted with ethyl acetate (3×100 mL). The combined organic layers were washed with brine, dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated and the residue was purified by silica gel column chromatography (2.5% ethyl acetate in petroleum ether) to give the desired product (6.7 g, 47.9 mmol, yield=54%) as a yellow oil which was used in the next step without further purification. 1H NMR (400 MHz, CDCl3) δ ppm 5.66 (s, 2H), 4.18-4.10 (m, 2H), 3.16-3.05 (m, 2.66 (s, 2H), 2.63 (s, 2H), 1.29-1.24 (t, J=9.4, 3H). concentrated The residue was poured into water The resulting mixture was extracted with ethyl acetate (3×100 mL) The combined organic layers were washed with brine dried over anhydrous sodium sulfate filtered The filtrate was concentrated the residue was purified by silica gel column chromatography (2.5% ethyl acetate in petroleum ether)

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

実験手順: To a stirred solution of cyclopent-3-enecarboxylic acid (10 g, 89.3 mmol) in anhydrous ethanol (30 mL) was added sulfurous dichloride (15.9 g, 134 mmol) at 0° C. The reaction mixture was stirred at room temperature overnight and then concentrated. The residue was poured into water. The resulting mixture was extracted with ethyl acetate (3×100 mL). The combined organic layers were washed with brine, dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated and the residue was purified by silica gel column chromatography (2.5% ethyl acetate in petroleum ether) to give the desired product (6.7 g, 47.9 mmol, yield=54%) as a yellow oil which was used in the next step without further purification. 1H NMR (400 MHz, CDCl3) δ ppm 5.66 (s, 2H), 4.18-4.10 (m, 2H), 3.16-3.05 (m, 2.66 (s, 2H), 2.63 (s, 2H), 1.29-1.24 (t, J=9.4, 3H). concentrated The residue was poured into water The resulting mixture was extracted with ethyl acetate (3×100 mL) The combined organic layers were washed with brine dried over anhydrous sodium sulfate filtered The filtrate was concentrated the residue was purified by silica gel column chromatography (2.5% ethyl acetate in petroleum ether)

反応条件: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A flame-dried 500 mL flask was charged with 2,6-dibromophenol (1.20 g, 4.76 mmol), tungsten oxychloride (0.813 g, 2.38 mmol), and anhydrous toluene (25 mL). The resulting suspension was heated at reflux under nitrogen for 1 h, and then the solvent was evaporated in vacuo. The solid residue was broken up with a spatula and dried in vacuo for 30 min. To the residue were added toluene (160 mL), Et4Pb (1.54 g, 4.76 mL), and 702 (22 g, 131.0 mmol). The mixture was heated at 90° C. under nitrogen for 1.5 h. After being cooled to r.t., the mixture was filtered through a celite, and the celite was rinsed with t-BuOMe. The combined filtrates were washed with 1% NaOH soln, water, and brine, and concentrated by evaporation at reduced pressure. The residue was distilled (37-38° C./1 Torr) to give 13.06 g (71%) of 703 as a colorless liquid. 1H NMR (400 MHz, CDCl3) δ 5.67 (s, 2H, CH═CH), 4.14 (q, 2H, J=7.2 Hz, OCH2), 3.11 (pentuplet, J=7.6 Hz, 1H, CH), 2.65 (d, J=7.6 Hz, 4H, 2CH2), 1.27 (t, J=7.2 Hz, 3H, CH3). The resulting suspension was heated at reflux under nitrogen for 1 h the solvent was evaporated in vacuo dried in vacuo for 30 min After being cooled to r.t. the mixture was filtered through a celite the celite was rinsed with t-BuOMe The combined filtrates were washed with 1% NaOH soln water, and brine, and concentrated by evaporation at reduced pressure The residue was distilled (37-38° C./1 Torr)

反応条件: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A flame-dried 500 ml flask was charged with 2,6-dibromophenol (1.20 g, 4.76 mmol), tungsten oxychloride (0.813 g, 2.38 mmol), and anhydrous toluene (25 mL). The resulting suspension was heated at reflux under nitrogen for 1 h, and then the solvent was evaporated in vacuo. The solid residue was broken up with a spatula and dried in vacuo for 30 min. To the residue were added toluene (160 mL), Et4Pb (1.54 g, 4.76 mL), and 702 (22 g, 131.0 mmol). The mixture was heated at 90° C. under nitrogen for 1.5 h. After being cooled to r.t., the mixture was filtered through a celite, and the celite was rinsed with t-BuOMe. The combined filtrates were washed with 1% NaOH soln, water, and brine, and concentrated by evaporation at reduced pressure. The residue was distilled (37-38° C./1 Torr) to give 13.06 g (71%) of 703 as a colorless liquid. 1H NMR (400 MHz, CDCl3) 65.67 (s, 2H, CH═CH), 4.14 (q, 2H, J=7.2 Hz, OCH2), 3.11 (pentuplet, J=7.6 Hz, 1H, CH), 2.65 (d, J=7.6 Hz, 4H, 2 CH2), 1.27 (t, J=7.2 Hz, 3 H, CH3). The resulting suspension was heated at reflux under nitrogen for 1 h the solvent was evaporated in vacuo dried in vacuo for 30 min After being cooled to r.t. the mixture was filtered through a celite the celite was rinsed with t-BuOMe The combined filtrates were washed with 1% NaOH soln water, and brine, and concentrated by evaporation at reduced pressure The residue was distilled (37-38° C./1 Torr)

反応条件: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A flame-dried 500 mL flask was charged with 2,6-dibromophenol (1.20 g, 4.76 mmol), tungsten oxychloride (0.813 g, 2.38 mmol), and anhydrous toluene (25 mL). The resulting suspension was heated at reflux under nitrogen for 1 h, and then the solvent was evaporated in vacuo. The solid residue was broken up with a spatula and dried in vacuo for 30 min. To the residue were added toluene (160 mL), Et4Pb (1.54 g, 4.76 mL), and 702 (22 g, 131.0 mmol). The mixture was heated at 90° C. under nitrogen for 1.5 h. After being cooled to r.t., the mixture was filtered through a celite, and the celite was rinsed with t-BuOMe. The combined filtrates were washed with 1% NaOH soln, water, and brine, and concentrated by evaporation at reduced pressure. The residue was distilled (37-38° C./1 Torr) to give 13.06 g (71%) of 703 as a colorless liquid. 1H NMR (400 MHz, CDCl3) δ 5.67 (s, 2H, CH═CH), 4.14 (q, 2H, J= 7.2 Hz, OCH2), 3.11 (pentuplet, J=7.6 Hz, 1H, CH), 2.65 (d, J=7.6 Hz, 4H, 2 CH2), 1.27 (t J=7.2 Hz, 3H, CH3). The resulting suspension was heated at reflux under nitrogen for 1 h the solvent was evaporated in vacuo dried in vacuo for 30 min After being cooled to r.t. the mixture was filtered through a celite the celite was rinsed with t-BuOMe The combined filtrates were washed with 1% NaOH soln water, and brine, and concentrated by evaporation at reduced pressure The residue was distilled (37-38° C./1 Torr)

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

実験手順: A solution containing 84.6 g of N-methylmorpholine N-oxide, 1 g of osmium tetroxide, 230 ml of water and 115 ml of acetone was allowed to stir for 30 minutes at room temperature. To this stirred mixture was added, very slowly over at least 8 hours, a solution of 80 g of ethyl 3-cyclopentene-1-carboxylate in 115 ml of acetone. The stirred mixture was heated at 50° C. for 2 hours to complete the reaction (verified by TLC examination using ethyl acetate/hexane 70/30). Sodium bisulfite (~10 g) was added, the stirring continued for a further 15 minutes, and the mixture filtered through Celite. The pH of the filtrate was adjusted to 7 by the addition of 12 N sulfuric acid (37 ml), the acetone evaporated, the pH of the residual solution adjusted to 2 with 12 N sulfuric acid (13 ml) and the solution extracted with ethyl acetate (4×250 ml). Evaporation of the dried ethyl acetate solution gave 4-ethoxycarbonyl-1,2-cyclopentanediol. To this stirred mixture was added, very slowly over at least 8 hours The stirred mixture was heated at 50° C. for 2 hours the stirring continued for a further 15 minutes the mixture filtered through Celite The pH of the filtrate was adjusted to 7 by the addition of 12 N sulfuric acid (37 ml) the acetone evaporated the solution extracted with ethyl acetate (4×250 ml) Evaporation of the dried ethyl acetate solution