2-Propenoic acid, 3-(1-pyrrolidinyl)-, ethyl ester, (2E)-

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: A solution of 29.43 g of ethyl propiolate (0.30 mol) in 200 ml of benzene was held at 25° in a water bath with magnetic stirring. A solution of 21.34 g of pyrrolidine in 50 ml of benzene was added dropwise over a period of 45 minutes, during which time the temperature rose to 35°. The clear brown solution was stirred overnight and the solvent under reduced pressure at 55°. The residue was distilled under reduced pressure to give 35.05 g of yellow oil, boiling point 110° (0.4 torr), which crystallized upon standing. The yellow solid was recrystallized from petroleum ether to give 31.36 (62%) of yellowish platelets, m.p. 37.5°-39.5°. rose to 35° at 55° The residue was distilled under reduced pressure

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

実験手順: A solution of 29.43 g of ethyl propiolate (0.30 mol) in 200 ml of benzene was held at 25° in a water bath with magnetic stirring. A solution of 21.34 g of pyrrolidine in 50 ml of benzene was added dropwise over a period of 45 minutes, during which time the temperature rose to 35°. The clear brown solution was stirred overnight and the solvent under reduced pressure at 55°. The residue was distilled under reduced pressure to give 35.05 g of yellow oil, boiling point 110° (0.4 torr), which crystallized upon standing. The yellow solid was recrystallized from petroleum ether to give 31.36 (62%) of yellowish platelets, m.p. 37.5°-39.5°. rose to 35° at 55° The residue was distilled under reduced pressure

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 N-hydroxy-2-methylbenzenecarboximidoyl chloride (2.07 g, 12.2 mmol, 1.0 equiv) in diethyl ether (15 mL) was added a solution of 3-pyrrolidin-1-yl-acrylic acid ethyl ester (prepared according to the procedure described in U.S. Pat. No. 4,187,099) (2.06 g, 12.2 mmol, 1.0 equiv) and triethylamine (1.48 g, 12.2 mmol, 1.0 equiv) in diethyl ether (30 mL) dropwise over 15 minutes. The resultant mixture was stirred at ambient temperature for 16 hours, partitioned between water and diethyl ether and separated. The aqueous phase was extracted with diethyl ether (2×), and the combined ethereal extracts were dried over anhydrous sodium sulfate, filtered, and concentrated under vacuum. Purification by flash column chromatography on silica gel (gradient: 0 to 20% ethyl acetate in cyclohexane) gave 1.32 g (47%) of 3-o-tolyl-isoxazole-4-carboxylic acid ethyl ester. 1H NMR (400 MHz, CDCl3) δ: 9.02 (s, 1H), 7.39-7.34 (m, 1H), 7.32-7.24 (m, 3H), 4.19 (q, 2H), 2.23 (s, 3H), 1.17 (t, 3H). prepared partitioned between water and diethyl ether separated The aqueous phase was extracted with diethyl ether (2×) the combined ethereal extracts were dried over anhydrous sodium sulfate filtered concentrated under vacuum Purification by flash column chromatography on silica gel (gradient: 0 to 20% ethyl acetate in cyclohexane)

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

実験手順: A solution of 29.43 g of ethyl propiolate (0.30 mol) in 200 ml of benzene was held at 25° in a water bath with magnetic stirring. A solution of 21.34 g of pyrrolidine in 50 ml of benzene was added dropwise over a period of 45 minutes, during which time the temperature rose to 35°. The clear brown solution was stirred overnight and the solvent removed under reduced pressure at 55°. The residue was distilled under pressure to give 35.05 g of yellow oil, boiling point 110° (0.4 torr), which crystallized upon standing. The yellow solid was recrystallized from petroleum ether to give 31.36 (62%) of yellowish platelets, m.p. 37.5°-39.5°. rose to 35° the solvent removed under reduced pressure at 55° The residue was distilled under pressure

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

実験手順: A solution of 29.43 g of ethyl propiolate (0.30 mol) in 200 ml of benzene was held at 25° in a water bath with magnetic stirring. A solution of 21.34 g of pyrrolidine in 50 ml of benzene was added dropwise over a period of 45 minutes, during which time the temperature rose to 35°. The clear brown solution was stirred overnight and the solvent removed under reduced pressure at 55°. The residue was distilled under pressure to give 35.05 g of yellow oil, boiling point 110° (0.4 torr), which crystallized upon standing. The yellow solid was recrystallized from petroleum ether to give 31.36 (62%) of yellowish platelets, m.p. 37.5°-39.5°. rose to 35° the solvent removed under reduced pressure at 55° The residue was distilled under pressure

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 solution of 1,1,2,2-tetrafluoroethyldimethylamine (3.2 g, 22 mmol) in diethyl ether (10 ml) and dioxane (10 ml) was added dropwise, under a nitrogen atmosphere, at a temperature of from 0 to 5° C., a solution of BF3-etherate (49% BF3, 5.6 ml, 44 mmol). After the addition had ended, the reaction mixture was stirred for 5 min. Subsequently, pyridine (1.7 g, 22 mmol) and a solution of ethyl 3-(pyrrolidin-1-yl)acrylate (2.9 g, 20 mmol) in dioxane (2 ml) were successively added dropwise to the reaction mixture at a temperature of from 0 to 5° C. After stirring for 6 hours, the reaction mixture was added at a temperature of from 0 to 5° C. to a mixture of sodium hydroxide (4.4 g, 110 mmol) and methylhydrazine (1.4 g, 30 mmol) in water (75 ml), and then the mixture was stirred at room temperature for 3 h. The reaction mixture was freed of volatile constituents. The resulting residue was taken up in water (50 ml), washed with ethyl acetate and then brought to a pH of 2 with conc. hydrochloric acid. The aqueous phase was decanted off and discarded. The resulting slimy residue was taken up in a mixture of tetrahydrofuran and methyl tert-butyl ether, dried over sodium sulfate, filtered and freed from the solvent under reduced pressure. 3-Difluoromethyl-1-methylpyrazole-4-carboxylic acid was obtained as a mixture with 5-difluoromethyl-1-methylpyrazole-4-carboxylic acid with a ratio of 2:1 in a yield of 60%. After the addition After stirring for 6 hours the mixture was stirred at room temperature for 3 h washed with ethyl acetate The aqueous phase was decanted off The resulting slimy residue was taken up in a mixture of tetrahydrofuran and methyl tert-butyl ether dried over sodium sulfate filtered

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

実験手順: A solution of 29.43 g of ethyl propiolate (0.30 mol) in 200 ml of benzene was held at 25° in a water bath with magnetic stirring. A solution of 21.34 g of pyrrolidine in 50 ml of benzene was added dropwise over a period of 45 minutes, during which time the temperature rose to 35°. The clear brown solution was stirred overnight and the solvent removed under reduced pressure at 55°. The residue was distilled under reduced pressure to give 35.05 g of yellow oil, boiling point 110° (0.4 torr), which crystallized upon standing. The yellow solid was recrystallized from petroleum ether to give 31.36 (62%) of yellowish platelets, m.p. 37.5°-39.5°. rose to 35° the solvent removed under reduced pressure at 55° The residue was distilled under reduced pressure

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

実験手順: A solution of 29.43 g of ethyl propiolate (0.30 mol) in 200 ml of benzene was held at 25° in a water bath with magnetic stirring. A solution of 21.34 g of pyrrolidine in 50 ml of benzene was added dropwise over a period of 45 minutes, during which time the temperature rose to 35°. The clear brown solution was stirred overnight and the solvent under reduced pressure at 55°. The residue was distilled under reduced pressure to give 35.05 g of yellow oil, boiling point 110° (0.4 torr), which crystallized upon standing. The yellow solid was recrystallized from petroleum ether to give 31.36 (62%) of yellowish platelets, m.p. 37.5°-39.5°. rose to 35° at 55° The residue was distilled under reduced pressure

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 N-hydroxy-2-methylbenzenecarboximidoyl chloride (2.07 g, 12.2 mmol, 1.0 equiv) in diethyl ether (15 mL) was added a solution of 3-pyrrolidin-1-yl-acrylic acid ethyl ester (prepared according to the procedure described in U.S. Pat. No. 4,187,099) (2.06 g, 12.2 mmol, 1.0 equiv) and triethylamine (1.48 g, 12.2 mmol, 1.0 equiv) in diethyl ether (30 mL) dropwise over 15 minutes. The resultant mixture was stirred at ambient temperature for 16 hours, partitioned between water and diethyl ether and separated. The aqueous phase was extracted with diethyl ether (2×), and the combined ethereal extracts were dried over anhydrous sodium sulfate, filtered, and concentrated under vacuum. Purification by flash column chromatography on silica gel (gradient: 0 to 20% ethyl acetate in cyclohexane) gave 1.32 g (47%) of 3-o-tolyl-isoxazole-4-carboxylic acid ethyl ester. 1H NMR (400 MHz, CDCl3) δ: 9.02 (s, 1H), 7.39-7.34 (m, 1H), 7.32-7.24 (m, 3H), 4.19 (q, 2H), 2.23 (s, 3H), 1.17 (t, 3H). prepared partitioned between water and diethyl ether separated The aqueous phase was extracted with diethyl ether (2×) the combined ethereal extracts were dried over anhydrous sodium sulfate filtered concentrated under vacuum Purification by flash column chromatography on silica gel (gradient: 0 to 20% ethyl acetate in cyclohexane)

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

実験手順: A solution of 29.43 g of ethyl propiolate (0.30 mol) in 200 ml of benzene was held at 25° in a water bath with magnetic stirring. A solution of 21.34 g of pyrrolidine in 50 ml of benzene was added dropwise over a period of 45 minutes, during which time the temperature rose to 35°. The clear brown solution was stirred overnight and the solvent removed under reduced pressure at 55°. The residue was distilled under pressure to give 35.05 g of yellow oil, boiling point 110° (0.4 torr), which crystallized upon standing. The yellow solid was recrystallized from petroleum ether to give 31.36 (62%) of yellowish platelets, m.p. 37.5°-39.5°. rose to 35° the solvent removed under reduced pressure at 55° The residue was distilled under pressure