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With hydrogenchloride; potassium tert-butylate; dimethyl sulfoxide; In cyclohexane; ethyl acetate; tert-butyl alcohol;
1a. Methyl [2-(1-(4-chlorophenyl)-3-pyrazolyloxy)pyridin-3-yl]glyoxylate At 60° C., 4.7 g (42 mmol) of potassium tert-butoxide were added a little at a time to a solution of 7.4 g (38.1 mmol) of <strong>[76205-19-1]1-(4-chlorophenyl)-3-hydroxypyrazole</strong> in 15 ml of tert-butanol. The mixture was stirred at this temperature for 1 hour and the solvent was then removed under reduced pressure. The residue was dissolved in 25 ml of abs. dimethyl sulfoxide, and a solution of 8.0 g (38.1 mmol) of methyl (2-chloropyridin-3-yl)glyoxylate in 10 ml of abs. dimethyl sulfoxide was then added at such a rate that the temperature did not exceed 30° C. After 30 minutes at room temperature, 50 ml of 0.5 N HCl were added and the reaction mixture was extracted repeatedly with ethyl acetate. The combined organic phases were washed with water and dried over sodium sulfate. The solvent was subsequently removed under reduced pressure. The resulting residue was purified by silica gel column chromatography using cyclohexane/ethyl acetate (10:1) as eluant. 5.5 g (40percent) of the title compound were obtained as a clear oil.
(ortho-[1-{4-chlorophenyl}-pyrazol-3-yl-oxymethyl]-phenyl)(5,6-dihydro-[1,4,2]dioxazin-3-yl)methanone O-methyl oxime[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
In N-methyl-acetamide; water;
Example 3 Synthesis of (ortho-[1-{4-chlorophenyl}-pyrazol-3-yl-oxymethyl]- phenyl)(5,6-dihydro-[1,4,2]dioxazin-3-yl)methanone O-methyl oxime A solution of 0.97 g of <strong>[76205-19-1]1-(para-chlorophenyl)-3-hydroxypyrazole</strong> in 20 ml of anhydrous dimethylformamide (DMF) was admixed with 0.13 g of sodium hydride and then stirred at 20-25 ° C. for approximately one hour. 1.34 g of the oxime from Example 2 were then added and the mixture was stirred at 60° C. for approximately three hours and then at 20-25° C. for approximately 14 hours. 300 ml of water were added and the mixture was then extracted with methyl tert-butyl ether (MTBE). The combined organic phases were washed with water and dried, and the solvent was then removed. The residue was chromatographed over silica gel (cyclohexane/ethyl acetate mixture [1:1]), giving 1.15 g of the title compound as a light-beige amorphous powder of m.p. 56-59° C. IR [cm-1]: 1546, 1502, 1480, 1464, 1358, 1093, 1054, 998, 935, 906.
13. Preparation of 1-(4-chlorophenyl)-3-hydroxypyrazole using pure oxygen with Co(II) catalysis 900 g of a 6.9percent strength solution of 1-(4-chlorophenyl)-pyrazolidin-3-one in 5percent strength potassium hydroxide solution were admixed with 600 mg of cobalt(II) acetate and oxygen was passed into the solution at room temperature via a capillary in such a manner that it was just completely absorbed. After approximately 30 min, the reaction was complete according to HPLC monitoring, the temperature having increased to 40° C. 908 g of a solution were obtained which had a 1-(4-chlorophenyl)-3-hydroxypyrazole content of 6.7percent.
With iron(III) chloride; acetic acid; at 50℃; for 4h;
First, 60 g of acetic acid was added to the apparatus,19.66 g (0.1 mol) of 1- (4-chlorophenyl) pyrazolidin-3-one was added with stirring,0.0162 g (0.0001 mol) of ferric chloride, and the temperature was raised to 50 C,4h after removing most of the solvent, add water, stirring, a large number of product precipitation,With sodium hydroxide solution to adjust the pH value to 7, continue stirring 0.5h,The yield was 99.7% and the content was 99.6% (LC), which was obtained by filtration to obtain 19.4 g of 1- (4-chlorophenyl) -3-pyrazolol.
91.2%
With dipotassium peroxodisulfate; sulfuric acid; In acetonitrile; for 6h;Reflux;
With a mechanical stir,Reflux condenser and a thermometer in a 250 ml four-necked reaction flask were charged with 19.6 g (0.1 mol)1- (4-chlorophenyl) pyrazolidin-3-one and 100 ml of acetonitrile,After stirring and dissolving,2 g (0.02 mol) of concentrated sulfuric acid and 32.4 g were added(0.12 mil) potassium persulfate,In 30-80 C (the optimum temperature of 75-80 C) heating reflux 6h,Most of the solvent B is distilled offNitrile,Cooled by adding 50 ml of water,With hydrochloric acid to adjust the pH to 1,Filtered and dried to obtain 17.7 g of product,Yield 91.2%.
84.2%
With hydrogenchloride; sodium nitrite; In water; for 3h;Inert atmosphere; Cooling with ice;
Under a nitrogen atmosphere, 0.80 g of 1-(4- chlorophenyl)pyrazolidin-3-one, 1.03 g of concentrated hydrochloric acid, and 3.0 g of water were mixed and ice-cooled. To this mixture, an aqueous solution prepared by dissolving 565.8 mg of sodium nitrite in 1.14 g of water was added dropwise. The obtained mixture was stirred with ice-cooling for 3 hours, water was added, and then the solid was collected by filtration. The obtained solid was washed with water and then hexane, followed by drying to give 0.80 g of 4-chlorophenyl-1H-pyrazol-3-ol (content: 83.3 wt %). Yield: 84.1%.
With potassium hydroxide; potassium hexacyanoferrate(III); In water;
6. Preparation of 1-(4-chlorophenyl)-3-hydroxypyrazole using air with potassium hexacyanoferrate(III) catalysis 98.3 g of 1-(4-chlorophenyl)pyrazolidin-3-one were dissolved in a mixture of 641.3 g of water and 33.75 g of potassium hydroxide and 0.98 g of potassium hexacyanoferrate(III) were added. The mixture was heated to 80 C., passing in a vigorous air stream through a capillary, and was then further oxidized at this temperature. After cooling, the mixture was acidified to pH 2 with concentrated sulfuric acid. The solid separating off was filtered off with suction, washed with water and diisopropyl ether and dried. 76 g of a light-brown solid remained.
With acetic acid; In water;
8. Preparation of 1-(4-chlorophenyl)-3-hydroxypyrazole using pure oxygen without catalysis under pressure The solution of 9.75 g of 1-(4-chlorophenyl)pyrazolidin-3-one in 150 g of water was charged into a 300 ml autoclave. Oxygen at 15 bar was then forced in; the mixture was heated to 50 C. and allowed to stand for six hours at this temperature. The mixture was cooled and adjusted to a pH of 5 by adding acetic acid. The solid which precipitated out was filtered off with suction, digested in water for 30 minutes at 60 C., and again filtered off with suction and dried. 9.4 g of the product remained as colorless powder having a content of 95.4%.
In potassium hydroxide;
12. Preparation of 1-(4-chlorophenyl)-3-hydroxypyrazole using pure oxygen without catalysis 850 g of a 7.4% strength solution of 1-(4-chlorophenyl)-pyrazolidin-3-one in 5% strength potassium hydroxide solution were heated to 60 C. oxygen was introduced into the solution via a capillary in such a manner that it was just completely absorbed. After approximately 90 min, the reaction was complete according to monitoring by HPLC. 855 g of a solution were obtained which had a 1-(4-chlorophenyl)-3-hydroxypyrazole content of 7.3%.
In potassium tert-butylate; water; tert-butyl alcohol;
1.b 1-(4-Chlorophenyl)-3-hydroxypyrazole A solution of 57.5 g of 4-chlorophenylhydrazine hydrosulfate in 1,000 ml of tert-butanol was first treated in portions with 100.8 g of potassium tert-butoxide and then (after stirring for 10 min) in the course of 45 min at 45° C.-50° C. with a solution of 27.7 g of methyl propiolate in 90 ml of tertbutanol. After 1 h at boiling point, the mixture was allowed to cool and the solvent was removed under reduced pressure. The residue thus obtained was dissolved in 1,200 ml of water. The aqueous phase was first washed with methylene chloride and then acidified, the product being deposited as a solid. 47.6 g of the title compound were obtained, m.p.: 185°-187° C.
With potassium carbonate; In N,N-dimethyl-formamide; at 50℃;
Example 12; /S/-{2-[/S/'-(4-chloro-phenyl)-pyrazol-3'-oxymethyl]-phenyl}-A/-methoxy-carbamic acid methyl ester; A/-Carbomethoxy-A/-methoxy-(2-chloromethyl)-aniline (0.20 g, 0.87 mmol), 1 -(4-chloro- phenyl)-3-hydroxypyrrazole (0.17 g, 0.87 mmol) and K2CO3 were suspended in DMF (10 ml). The reaction mixture was stirred at 50 °C overnight. Thin layer chromatography control showed complete consumption of both starting materials. The suspension was diluted with tert-butyl methyl ether (100 ml), extracted four times with water and dried over MgSC . The crude product could be optionally purified by column chromatography on S1O2 to give the desired product (0.25 g, 0.64 mmol, 74percent yield). Alternatively, the product could be purified by recrystallization from ethanol/hbO (3:1 (v/v)).
74%
With potassium carbonate; In N,N-dimethyl-formamide; at 50℃;
Example 12N-{2-[N'-(4-chloro-phenyl)-pyrazol-3'-oxymethyl]-phenyl}-N-methoxy-carbamic acid methyl esterN-Carbomethoxy-N-methoxy-(2-chloromethyl)-aniline (0.20 g, 0.87 mmol), 1-(4-chloro-phenyl)-3-hydroxypyrrazole (0.17 g, 0.87 mmol) and K2CO3 were suspended in DMF (10 ml). The reaction mixture was stirred at 50° C. overnight. Thin layer chromatography control showed complete consumption of both starting materials. The suspension was diluted with tert-butyl methyl ether (100 ml), extracted four times with water and dried over MgSO4. The crude product could be optionally purified by column chromatography on SiO2 to give the desired product (0.25 g, 0.64 mmol, 74percent yield). Alternatively, the product could be purified by recrystallization from ethanol/H2O (3:1 (v/v)).
With thionyl chloride; N,N-dimethyl-formamide;Reflux;
General procedure: A mixture of SOCl2 (5 mL), Ia?Id (1.0 mmol), and a catalytic amount of DMF (0.1 mmol) wereheated under reflux for about 4 h (monitored by TLC), then excess SOCl2 was evaporated and H2O(200 mL) was added with good stirring. The precipitate that formed was filtered off, washed with H2O, andthen purified by a silica-gel column chromatography (petroleum ether/EtOAc = 5:1) to afford IIa?IId.
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