ethyl 4,4-dimethyl-3-oxopentanoate

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: A suspension of 21.6 g (0.4 mol) of sodium methylate, 19.4 g (0.2 mol) of acetamidine hydrochloride, 34.4 g (0.2 mol) of pivaloylacetic acid ethyl ester and 100 ml of methanol was heated for 10 hours under reflux and then evaporated, and the residue was taken up in 350 ml of water. Concentrated hydrochloric acid was added to the aqueous solution, while cooling with ice, to a pH of about 6, and the mixture was then extracted twice with 200 ml of methylene chloride each time. The combined methylene chloride extracts were dried over sodium sulphate and then concentrated. 21 g (63% of theory) of 2-methyl-4-hydroxy-6-tert.-butyl-pyrimidine were obtained in the form of colorless crystals of melting point 131°-132° C. was heated for 10 hours under reflux evaporated Concentrated hydrochloric acid was added to the aqueous solution while cooling with ice, to a pH of about 6 the mixture was then extracted twice with 200 ml of methylene chloride each time The combined methylene chloride extracts were dried over sodium sulphate concentrated

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

実験手順: A suspension of 21.6 g (0.4 mol) of sodium methylate, 19.4 g (0.2 mol) of acetamidine hydrochloride, 34.4 g (0.2 mol) of pivaloylacetic acid ethyl ester and 100 ml of methanol was heated for 10 hours under reflux and then evaporated, and the residue was taken up in 350 ml of water. Concentrated hydrochloric acid was added to the aqueous solution, while cooling with ice, to a pH of about 6, and the mixture was then extracted twice with 200 ml of methylene chloride each time. The combined methylene chloride extracts were dried over sodium sulphate and then concentrated. 21 g (63% of theory) of 2-methyl-4-hydroxy-6-tert.-butyl-pyrimidine were obtained in the form of colorless crystals of melting point 131°-132° C. was heated for 10 hours under reflux evaporated Concentrated hydrochloric acid was added to the aqueous solution while cooling with ice, to a pH of about 6 the mixture was then extracted twice with 200 ml of methylene chloride each time The combined methylene chloride extracts were dried over sodium sulphate concentrated

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

実験手順: 1.0 kg of ethyl pivaloylacetate was dissolved in 2.5 liters of ethanol and 320 g of hydrazine hydrate was dropwise added thereto with cooling with water. After the completion of the dropwise addition, the whole was reacted overnight at room temperature, and then 5.0 liters of water was added thereto and stirred. The crystal which precipitated was filtered under reduced pressure, washed well with water and then with a small amount of methanol, and then dried with air. Yield: 812 g, 98.5%. After the completion of the dropwise addition the whole was reacted overnight at room temperature The crystal which precipitated was filtered under reduced pressure washed well with water with a small amount of methanol, and then dried with air

反応条件: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Sodium pellets (4.6 g, 200 mmol) were dissolved in ethanol (165 ml) under nitrogen at room temperature and a solution of diethyloxalate (27.2 ml, 200 mmol) in tert-butyl-methyl ketone (20.1 g, 200 mmol) was added dropwise at room temperature over 15 minutes. The reaction was diluted with ethanol (100 ml), heated to 60° C. and stirred at this temperature for 2 hours. After cooling to room temperature the reaction was stirred for 64 hours, poured onto ice-cold 2N HCl (200 ml) and extracted with diethylether (3×200 ml). The combined organic extracts were washed with water, dried over MgSO4 and concentrated under reduced pressure to give 4,4-dimethyl-3-oxo-pentanoic acid ethyl ester (36.7 g) as a yellow oil. 1H NMR (400 MHz, CDCl3): δ=6.48 (1H, s), 4.26-4.37 (2H, quart), 1.29-1.38 (3H, t), 1.17 (9H, s) ppm. LRMS (electrospray): m/z [M+Na]+ 223, [M−H]+ 199. After cooling to room temperature the reaction was stirred for 64 hours poured onto ice-cold 2N HCl (200 ml) extracted with diethylether (3×200 ml) The combined organic extracts were washed with water dried over MgSO4 concentrated under reduced pressure

反応条件: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Sodium pellets (4.6 g, 200 mmol) were dissolved in ethanol (165 ml) under nitrogen at room temperature and a solution of diethyloxalate (27.2 ml, 200 mmol) in tert-butyl-methyl ketone (20.1 g, 200 mmol) was added dropwise at room temperature over 15 minutes. The reaction was diluted with ethanol (100 ml), heated to 60° C. and stirred at this temperature for 2 hours. After cooling to room temperature the reaction was stirred for 64 hours, poured onto ice-cold 2N HCl (200 ml) and extracted with diethylether (3×200 ml). The combined organic extracts were washed with water, dried over MgSO4 and concentrated under reduced pressure to give 4,4-dimethyl-3-oxo-pentanoic acid ethyl ester (36.7 g) as a yellow oil. 1H NMR (400 MHz, CDCl3): δ=6.48 (1H, s), 4.26-4.37 (2H, quart), 1.29-1.38 (3H, t), 1.17 (9H, s) ppm. LRMS (electrospray): m/z [M+Na]+ 223, [M−H]+ 199. After cooling to room temperature the reaction was stirred for 64 hours poured onto ice-cold 2N HCl (200 ml) extracted with diethylether (3×200 ml) The combined organic extracts were washed with water dried over MgSO4 concentrated under reduced pressure

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

実験手順: 9.2 g (0.2 mol) of methylhydrazine were added dropwise to a mixture of 34.4 g (0.2 mol) of pivaloylacetic acid ethyl ester, 10.8 g (0.2 mol) of sodium methylate and 100 ml of methanol at 20° C. When the exothermic reaction had subsided, the reaction mixture was heated for 2 hours under reflux and then concentrated, the residue was taken up in 200 ml of water and this solution was acidified with concentrated hydrochloric acid to a pH of ca. 6. The resulting precipitate was filtered off, dried and recrystallized from isopropanol. 27 g (87% of theory) of 1-methyl-3-tert.-butyl-5-hydroxy-pyrazole were obtained in the form of colorless crystals of melting point 150° C. When the exothermic reaction the reaction mixture was heated for 2 hours under reflux concentrated The resulting precipitate was filtered off dried recrystallized from isopropanol

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

実験手順: 583.7 g of hydroxylamine hydrochloride was dissolved in 2 l of a 4N aqueous solution of sodium hydroxide. 2 l of ethanol was added to the solution under cooling with ice. A 1:1 mixture of a 4N aqueous solution of sodium hydroxide and ethanol was added to the solution so that the pH thereof was adjusted to 10.0. 1,380 g of ethyl pivaloylacetate and a 1:1 mixture of a 4N aqueous solution of sodium hydroxide and ethanol were simultaneously added dropwise to the solution in such a manner that the pH of the reaction solution was 10±0.2 and the temperature thereof was 0° to 5° C. After the dropwise addition was finished, the reaction mixture was stirred at room temperature for 2 hours, and then poured into 6 kg of concentrated hydrochloric acid. The reaction mixture was allowed to stand for 12 hours. The resulting crystal was filtered off, thoroughly washed with water, and then dried. (Yield: 770 g (68.2%); m.p.: 99°-101° C.) under cooling with ice was added to the solution so that the pH were simultaneously added dropwise to the solution in such a manner that the pH of the reaction solution thereof was 0° to 5° C After the dropwise addition to stand for 12 hours The resulting crystal was filtered off thoroughly washed with water dried

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

実験手順: 2 g (7.4 mmol) of 4-benzenesulphonyl-5-methylsulphanyl-2H-pyrazol-3-ylamine and 2.91 ml (18.3 mmol) of ethyl pivaloylacetate were added to 27 g of polyphosphoric acid and heated to 120° for 5 hrs. After cooling 100 ml of water were slowly added thereto and the mixture was extracted three times with CH2Cl2. The organic phase was dried (MgSO4), filtered and evaporated. Chromatography (SiO2, CH2Cl2/EtOAc) yielded 1.34 g (48%) of 3-benzenesulphonyl-5-tert-butyl-2-methylsulphanyl-pyrazolo[1,5-a]pyrimidin-7-ol as a colorless foam. heated to 120° for 5 hrs were slowly added the mixture was extracted three times with CH2Cl2 The organic phase was dried (MgSO4) filtered evaporated

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

実験手順: 2 g (7.4 mmol) of 4-benzenesulphonyl-5-methylsulphanyl-2H-pyrazol-3-ylamine and 2.91 ml (18.3 mmol) of ethyl pivaloylacetate were added to 27 g of polyphosphoric acid and heated to 120° for 5 hrs. After cooling 100 ml of water were slowly added thereto and the mixture was extracted three times with CH2Cl2. The organic phase was dried (MgSO4), filtered and evaporated. Chromatography (SiO2, CH2Cl2/EtOAc) yielded 1.34 g (48%) of 3-benzenesulphonyl-5-tert-butyl-2-methylsulphanyl-pyrazolo[1,5-a]pyrimidin-7-ol as a colorless foam. heated to 120° for 5 hrs were slowly added the mixture was extracted three times with CH2Cl2 The organic phase was dried (MgSO4) filtered evaporated

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

実験手順: 9.2 g (0.2 mol) of methylhydrazine were added dropwise to a mixture of 34.4 g (0.2 mol) of pivaloylacetic acid ethyl ester, 10.8 g (0.2 mol) of sodium methylate and 100 ml of methanol at 20° C. After the exothermic reaction had subsided, the mixture was heated for two hours under reflux. The reaction mixture was then concentrated, the residue was taken up in 200 ml of water and this solution was acidified to pH 6 with concentrated hydrochloric acid. The resulting precipitate was filtered off, dried and recrystallized from isopropanol. 27 g (87% of theory) of 1-methyl-3-tert.-butyl-5-hydroxy-pyrazole were obtained in the form of colorless crystals with a melting point of 150° C. After the exothermic reaction the mixture was heated for two hours under reflux The reaction mixture was then concentrated The resulting precipitate was filtered off dried recrystallized from isopropanol