(3-bromophenyl)hydrazine;hydrochloride

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

実験手順: Under anhydrous conditions a solution of 3-bromophenylhydrazine hydrochloride (22.5 g, 100 mmol) and 2,3-dihydrofuran (7.55 ml, 100 mmol) in 200 ml of dry THF was stirred at ambient temperature for 3 h. The reaction mixture was partitioned between EtOAc and H2O. The organic phase was washed with H2O and brine. After drying (Na2 SO4), the solvent was evaporated to give 25.6 g of the product as a brown oil. The product was of suitable purity for use in the next step. The reaction mixture was partitioned between EtOAc and H2O The organic phase was washed with H2O and brine After drying (Na2 SO4) the solvent was evaporated

反応条件: temp:-20.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of 7.10 g (35.5 mmol) of (E and/or Z)-3-methoxy-2-propionyl-pent-2-enoic acid methyl ester in 10 ml of MeOH was added to a solution of 8.09 g (35.5 mmol) of 3-bromophenylhydrazine hydrochloride in 150 ml of MeOH and the mixture was cooled to −20° C. To this mixture was added a solution of 3.79 g=5.22 ml (37.2 mmol) of Et3N in 40 ml of MeOH drop by drop and the reaction was then warmed up to RT. After 20 hours, it was poured into crashed ice and extracted twice with Et2O; the organic phases were washed with water, dried over magnesium sulfate, filtered and evaporated to give 7.62 g of the title compound as light red oil. MS: 337.1 (MH+, 1 Br). the reaction was then warmed up to RT it was poured extracted twice with Et2O the organic phases were washed with water dried over magnesium sulfate filtered evaporated

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

実験手順: To a suspension of 1-(3-bromophenyl)hydrazine hydrochloride (1.0 g, 4.47 mmol) in ethanol (8.9 mL) was added dropwise 2.0 M sodium ethoxide in ethanol (0.77 mL, 9.84 mmol, 2.2 eq.). Diethyl 2-methylmalonate (0.85 mL, 4.92 mmol, 1.1 eq.) was then added. The reaction mixture was stirred at 90° C. for 16 hours and then quenched with 2 N aqueous hydrochloric acid (50 mL). The reaction was extracted with ethyl acetate (3×50 mL), and the combined organic layers were dried (MgSO4), filtered, and evaporated under reduced pressure. Purification using MPLC (Biotage) eluted with 3:1 v/v ethyl acetate-hexane gave the desired product as a white solid (125 mg, 0.46 mmol, 10.4% yield). MS LC-MS (ES MH+=269/271); TLC (Rf=0.10, 50% ethyl acetate-hexane). quenched with 2 N aqueous hydrochloric acid (50 mL) The reaction was extracted with ethyl acetate (3×50 mL) the combined organic layers were dried (MgSO4) filtered evaporated under reduced pressure Purification eluted with 3:1 v/v ethyl acetate-hexane

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

実験手順: To a suspension of 1-(3-bromophenyl)hydrazine hydrochloride (1.0 g, 4.47 mmol) in ethanol (8.9 mL) was added dropwise 2.0 M sodium ethoxide in ethanol (0.77 mL, 9.84 mmol, 2.2 eq.). Diethyl 2-methylmalonate (0.85 mL, 4.92 mmol, 1.1 eq.) was then added. The reaction mixture was stirred at 90° C. for 16 hours and then quenched with 2 N aqueous hydrochloric acid (50 mL). The reaction was extracted with ethyl acetate (3×50 mL), and the combined organic layers were dried (MgSO4), filtered, and evaporated under reduced pressure. Purification using MPLC (Biotage) eluted with 3:1 v/v ethyl acetate-hexane gave the desired product as a white solid (125 mg, 0.46 mmol, 10.4% yield). MS LC-MS (ES MH+=269/271); TLC (Rf=0.10, 50% ethyl acetate-hexane). quenched with 2 N aqueous hydrochloric acid (50 mL) The reaction was extracted with ethyl acetate (3×50 mL) the combined organic layers were dried (MgSO4) filtered evaporated under reduced pressure Purification eluted with 3:1 v/v ethyl acetate-hexane

反応条件: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: (3-Bromophenyl)hydrazine hydrochloride (10 g, 44 mmol, 1 eq.), benzophenone (8.14 g, 44 mmol, 1 eq.) and ethanol (100 mL) are placed in a 250 mL round-bottomed flask. 2 mL of concentrated sulfuric acid are then added. The resulting suspension is heated at a temperature in the region of 80° C. After 30 minutes at this temperature, the suspension becomes a solution. The solution is stirred at this temperature for 18 hours, and is then concentrated to 95%. The residue is diluted with ethyl acetate and washed with sodium hydrogen carbonate solution. After drying over magnesium sulfate, the solution is concentrated and the residue is purified by chromatography on a column of silica gel, eluting with an ether/heptane mixture (3/97 by volume). 15 g (95%) of N-benzhydrylidene-N′-(3-bromophenyl)hydrazine are thus obtained. is then concentrated to 95% The residue is diluted with ethyl acetate washed with sodium hydrogen carbonate solution After drying over magnesium sulfate the solution is concentrated the residue is purified by chromatography on a column of silica gel eluting with an ether/heptane mixture (3/97 by volume)

反応条件: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: (3-Bromophenyl)hydrazine hydrochloride (10 g, 44 mmol, 1 eq.), benzophenone (8.14 g, 44 mmol, 1 eq.) and ethanol (100 mL) are placed in a 250 mL round-bottomed flask. 2 mL of concentrated sulfuric acid are then added. The resulting suspension is heated at a temperature in the region of 80° C. After 30 minutes at this temperature, the suspension becomes a solution. The solution is stirred at this temperature for 18 hours, and is then concentrated to 95%. The residue is diluted with ethyl acetate and washed with sodium hydrogen carbonate solution. After drying over magnesium sulfate, the solution is concentrated and the residue is purified by chromatography on a column of silica gel, eluting with an ether/heptane mixture (3/97 by volume). 15 g (95%) of N-benzhydrylidene-N′-(3-bromophenyl)hydrazine are thus obtained. is then concentrated to 95% The residue is diluted with ethyl acetate washed with sodium hydrogen carbonate solution After drying over magnesium sulfate the solution is concentrated the residue is purified by chromatography on a column of silica gel eluting with an ether/heptane mixture (3/97 by volume)

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

実験手順: To a solution of 3-bromophenylhydrazine hydrochloride (2.25 g, 10.1 mmol) in acetic acid (15.1 mL) and water (5.04 mL) were added ethyl(ethoxymethylene)cyanoacetate (1.88 g, 11.1 mmol) and sodium acetate (3.02 g, 22.2 mmol), and the solution was refluxed for 16 hours. The reaction was cooled and quenched with ice-water. The precipitate formed was filtered, washed with water and dried under vacuum for 24 hours to give 2.95 g of the titled compound (93% yield). the solution was refluxed for 16 hours The reaction was cooled quenched with ice-water The precipitate formed was filtered washed with water dried under vacuum for 24 hours

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

実験手順: To a solution of 3-bromophenylhydrazine hydrochloride (2.25 g, 10.1 mmol) in acetic acid (15.1 mL) and water (5.04 mL) were added ethyl(ethoxymethylene)cyanoacetate (1.88 g, 11.1 mmol) and sodium acetate (3.02 g, 22.2 mmol), and the solution was refluxed for 16 hours. The reaction was cooled and quenched with ice-water. The precipitate formed was filtered, washed with water and dried under vacuum for 24 hours to give 2.95 g of the titled compound (93% yield). the solution was refluxed for 16 hours The reaction was cooled quenched with ice-water The precipitate formed was filtered washed with water dried under vacuum for 24 hours

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

実験手順: A solution of 3-bromophenylhydrazine hydrochloride (0.5 g, 2.2 mmol) and ethyl 5,5-dimethyl-2,4-dioxohexanoate (0.54 g, 2.68 mmol) in acetic acid (10 ml) was refluxed for 16 hours. The reaction was cooled to room temperature, and the solvent was removed under reduced pressure. The residue was partitioned between ethyl acetate and water. The organic layer was washed with water, saturated bicarbonate and brine, and dried over sodium sulfate, filtered and concentrated. The crude material was purified by column chromatography (4.8:0.2 hexanes/ethyl acetate) to give ethyl 1-(3-bromophenyl)-5-tert-butyl-1H-pyrazole-3-carboxylate (0.59 g, 74%) as a syrup. the solvent was removed under reduced pressure The residue was partitioned between ethyl acetate and water The organic layer was washed with water, saturated bicarbonate and brine dried over sodium sulfate filtered concentrated The crude material was purified by column chromatography (4.8:0.2 hexanes/ethyl acetate)

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

実験手順: A solution of 3-bromophenylhydrazine hydrochloride (2 g, 8.9 mmol) and ethyl-2,4-dioxovalerate (1.69 g, 10.7 mmol) in acetic acid (44 ml) was refluxed for 16 hours. The reaction was cooled to room temperature and concentrated under reduced pressure. The residue was partitioned between ethyl acetate and water. The organic layer was washed with water, saturated bicarbonate and brine, and then dried over sodium sulfate, filtered and concentrated in vacuo. The crude product, thus obtained, was purified by silica-gel column chromatography (4.8:0.2 hexanes/ethyl acetate) to give the product (2.34 g, 84%) as a syrup. concentrated under reduced pressure The residue was partitioned between ethyl acetate and water The organic layer was washed with water, saturated bicarbonate and brine dried over sodium sulfate filtered concentrated in vacuo The crude product, thus obtained was purified by silica-gel column chromatography (4.8:0.2 hexanes/ethyl acetate)

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

実験手順: A solution of 3-bromophenylhydrazine hydrochloride (2 g, 8.9 mmol) and ethyl-2,4-dioxovalerate (1.69 g, 10.7 mmol) in acetic acid (44 ml) was refluxed for 16 hours. The reaction was cooled to room temperature and concentrated under reduced pressure. The residue was partitioned between ethyl acetate and water. The organic layer was washed with water, saturated bicarbonate and brine, and then dried over sodium sulfate, filtered and concentrated in vacuo. The crude product, thus obtained, was purified by silica-gel column chromatography (4.8:0.2 hexanes/ethyl acetate) to give the product (2.34 g, 84%) as a syrup. concentrated under reduced pressure The residue was partitioned between ethyl acetate and water The organic layer was washed with water, saturated bicarbonate and brine dried over sodium sulfate filtered concentrated in vacuo The crude product, thus obtained was purified by silica-gel column chromatography (4.8:0.2 hexanes/ethyl acetate)

反応条件: temp:140.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A suspension of 3-bromophenylhydrazine hydrochloride (3.78 g, 17 mmol) in formamide (15 ml) was heated at 140° C. for 16 h. The reaction mixture was cooled to ambient temperature, diluted into dichloromethane (100 ml) and washed with water (2×100 ml). The organic phase was dried over anhydrous magnesium sulphate, filtered and evaporated to dryness to give 1-(3-bromophenyl)-1H-[1,2,4]triazole (3.44 g) as a tan solid: 1H NMR (400 MHz, CDCl3) δ 8.57 (1H, s), 8.11 (1H, s), 7.90 (1H, t, J 2 Hz), 7.62-7.64 (1H, m), 7.53-7.55 (1H, m), 7.38 (1H, t, J 8 Hz). The reaction mixture was cooled to ambient temperature washed with water (2×100 ml) The organic phase was dried over anhydrous magnesium sulphate filtered evaporated to dryness