butyl 2-hydroxyacetate

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:; See reaction.notes.procedure_details.

実験手順: n-Butyl glycolate (231 g; 1.75 mol) and imidazole (345.1 g; 5.07 mol) were combined at 0° C. The suspension obtained was treated portionwise with t-butyldimethylchlorosilane (303 g; 2.01 mol) over 1.5 hours. After 20 hours at room temperature the reaction mixture was diluted with ether/n-hexane 1:1 (1 l) and suction filtered. The crystals were rinsed thoroughly with ether/n-hexane 1:1 (200 ml). The filtrate was washed in succession with water (2×700 ml) and saturated aqueous sodium chloride solution (500 ml), dried over magnesium sulphate and concentrated. The oil obtained was distilled over a Vigreux column (7.5 cm). Yield: 405 g (94%) as a colorless oil (b.p. 78° C./0.98 mm Hg). were combined at 0° C The suspension obtained filtered The crystals were rinsed thoroughly with ether/n-hexane 1:1 (200 ml) The filtrate was washed in succession with water (2×700 ml) and saturated aqueous sodium chloride solution (500 ml) dried over magnesium sulphate concentrated The oil obtained was distilled over a Vigreux column (7.5 cm)

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:25.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of 3.4 g (0.01 mole) 4-chloro-3-(2,4-difluoro-5-nitrophenyl)-1-methyl-5-(trifluoro-methyl)-1H-pyrazole and 1.4 mL (0.011 mole) butyl glycolate in 25 mL anhydrous THF was chilled to 0° C. Maintaining the temperature below 5° C., 0.33 g (0.011 mole) NaH was added in portions. Once the addition was completed, the reaction mixture was allowed to warm to 25° C. After 3 hours the mixture was carefully quenched with water and extracted with ethyl acetate. The ethyl acetate extracts were washed with brine, dried over anhydrous MgSO4, and concentrated in vacuo. The residue was purified chromatographically with 20% ethyl acetate/hexanes to yield 3.25 g (72%) (4-(4-chloro-1-methyl-5-(trifluoromethyl)-1H-pyrazol-3-yl)-5-fluoro-2-nitrophenoxy)acetic acid, butyl ester as a light yellow solid; mp 65° C. was added in portions Once the addition After 3 hours the mixture was carefully quenched with water extracted with ethyl acetate The ethyl acetate extracts were washed with brine dried over anhydrous MgSO4 concentrated in vacuo The residue was purified chromatographically with 20% ethyl acetate/hexanes

反応条件: temp:25.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of 3.4 g (0.01 mole) 4-chloro-3-(2,4-difluoro-5-nitrophenyl)-1-methyl-5-(trifluoro-methyl)-1H-pyrazole and 1.4 mL (0.011 mole) butyl glycolate in 25 mL anhydrous THF was chilled to 0° C. Maintaining the temperature below 5° C., 0.33 g (0.011 mole) NaH was added in portions. Once the addition was completed, the reaction mixture was allowed to warm to 25° C. After 3 hours the mixture was carefully quenched with water and extracted with ethyl acetate. The ethyl acetate extracts were washed with brine, dried over anhydrous MgSO4, and concentrated in vacuo. The residue was purified chromatographically with 20% ethyl acetate/hexanes to yield 3.25 g (72%) (4-(4-chloro-1-methyl-5-(trifluoromethyl)-1H-pyrazol-3-yl)-5-fluoro-2-nitrophenoxy)acetic acid, butyl ester as a light yellow solid; mp 65° C. was added in portions Once the addition After 3 hours the mixture was carefully quenched with water extracted with ethyl acetate The ethyl acetate extracts were washed with brine dried over anhydrous MgSO4 concentrated in vacuo The residue was purified chromatographically with 20% ethyl acetate/hexanes

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

実験手順: A suspension of 3-chloro-2-(2,4-difluoro-5-nitrophenyl)-4,5,6,7-tetrahydro-2H-indazole (10 g), butyl glycollate (5 g) and potassium fluoride (10 g) in dioxane (30 g) was refluxed for 1 hour. After completion of the reaction, the reaction mixture was poured into water and extracted with ethyl acetate. The extract was dried over magnesium sulfate and concentrated. The residue was purified by liquid column chromatography using a mixture of hexane and ethyl acetate as an eluent to give 3-chloro-2-(2-fluoro-4-butyloxycarbonylmethoxy-5-nitro-phenyl)-4,5,6,7-tetrahydro-2H-indazole (10.2 g). m.p., 138°-139° C. was refluxed for 1 hour After completion of the reaction extracted with ethyl acetate The extract was dried over magnesium sulfate concentrated The residue was purified by liquid column chromatography a mixture of hexane and ethyl acetate as an eluent

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

実験手順: A suspension of 3-chloro-2-(2,4-difluoro-5-nitrophenyl)-4,5,6,7-tetrahydro-2H-indazole (10 g), butyl glycollate (5 g) and potassium fluoride (10 g) in dioxane (30 g) was refluxed for 1 hour. After completion of the reaction, the reaction mixture was poured into water and extracted with ethyl acetate. The extract was dried over magnesium sulfate and concentrated. The residue was purified by liquid column chromatography using a mixture of hexane and ethyl acetate as an eluent to give 3-chloro-2-(2-fluoro-4-butyloxycarbonylmethoxy-5-nitro-phenyl)-4,5,6,7-tetrahydro-2H-indazole (10.2 g). m.p., 138° -139° C. was refluxed for 1 hour After completion of the reaction extracted with ethyl acetate The extract was dried over magnesium sulfate concentrated The residue was purified by liquid column chromatography a mixture of hexane and ethyl acetate as an eluent

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

実験手順: Then, 1.10 g of 3-(4-fluoro-5-nitrophenyl)-1-methyl-6-trifluoromethyl-2-oxo-1,2-dihydropyrazine (present compound 1-13) was dissolved in 4.0 ml of 1,4-dioxane, to which 0.812 g of potassium fluoride and 0.925 g of butyl glycolate, and the mixture was heated under reflux for 1.5 hours. After completion of the reaction, the reaction mixture was left cooling to room temperature. The reaction mixture was poured into water, followed by extraction with ethyl acetate. The organic layer was washed with saturated sodium chloride solution, dried with anhydrous magnesium sulfate, and concentrated. The residue was subjected to silica gel column chromatography, which afforded 1.25 g (yield, 83%) of 3-[4-(butoxycarbonylmethoxy)-5-nitrophenyl]-1-methyl-6-trifluoromethyl-2-oxo-1,2-dihydropyrazine (the present compound depicted below). the mixture was heated under reflux for 1.5 hours After completion of the reaction the reaction mixture was left followed by extraction with ethyl acetate The organic layer was washed with saturated sodium chloride solution dried with anhydrous magnesium sulfate concentrated

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

実験手順: Then, 7.61 g of 3-(2,4-difluoro-5-nitrophenyl)-1-methyl-6-trifluoromethyl-2-oxo-1,2-dihydropyrazine (present compound 1-16) was dissolved in 10 ml of 1,4-dioxane, to which 5.28 g of potassium fluoride and 9.0 g of butyl glycolate were added, and the mixture was heated under reflux for 1.5 hours. After completion of the reaction, the reaction mixture was left cooling to room temperature. The reaction mixture was poured into water, followed by extraction with ethyl acetate. The organic layer was washed with saturated sodium chloride solution, dried with anhydrous magnesium sulfate, and concentrated. The residue was subjected to silica gel column chromatography, which afforded 8.37 g (yield, 82%) of 3-[4-(butoxycarbonylmethoxy)-2-fluoro5-nitrophenyl]-1-methyl-6-trifluoromethyl-2-oxo-1,2-dihydropyrazine (the present compound depicted below; m.p., 109.5° C.). ##STR40## were added the mixture was heated under reflux for 1.5 hours After completion of the reaction the reaction mixture was left followed by extraction with ethyl acetate The organic layer was washed with saturated sodium chloride solution dried with anhydrous magnesium sulfate concentrated

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

実験手順: Then, 7.61 g of 3-(2,4-difluoro-5-nitrophenyl)-1-methyl-6-trifluoromethyl-2-oxo-1,2-dihydropyrazine (present compound 1-16) was dissolved in 10 ml of 1,4-dioxane, to which 5.28 g of potassium fluoride and 9.0 g of butyl glycolate were added, and the mixture was heated under reflux for 1.5 hours. After completion of the reaction, the reaction mixture was left cooling to room temperature. The reaction mixture was poured into water, followed by extraction with ethyl acetate. The organic layer was washed with saturated sodium chloride solution, dried with anhydrous magnesium sulfate, and concentrated. The residue was subjected to silica gel column chromatography, which afforded 8.37 g (yield, 82%) of 3-[4-(butoxycarbonylmethoxy)-2-fluoro5-nitrophenyl]-1-methyl-6-trifluoromethyl-2-oxo-1,2-dihydropyrazine (the present compound depicted below; m.p., 109.5° C.). ##STR40## were added the mixture was heated under reflux for 1.5 hours After completion of the reaction the reaction mixture was left followed by extraction with ethyl acetate The organic layer was washed with saturated sodium chloride solution dried with anhydrous magnesium sulfate concentrated