4-(hydroxyiminomethyl)benzonitrile

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:4.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of DMF (262.0 L), 4-cyanobenzaldoxime (46 kg, 342.1 mol), and N-chlorosuccinimide (54 kg, 389.4 mol) was added isobutyl vinylacetate (95 kg. 665.7 mol). The solution was cooled to 2-6° C., and triethylamine (40 kg. 388.6 mol) was slowly added over a period of 4 h. The reaction was stirred at the same temperature for an addition 1 h. Water (330.0 L) and hydrochloric acid (1 N, 49 L) were added. The crude product was collected by filtration, washed with water (555.0 L), and redissolved in toluene (500.0 L, 40° C.). The organic layer was washed with water (291.0 L) and dried by azeotropic distillation (removing about 250 L of toluene). Heptane (300.0 L) was added, and the reaction was cooled at 0-5° C. for 3 h. The product was collected by filtration and washed with toluene/heptane (150.0 L, 1/2 ratio). The product was dried under vacuum at 55-60° C. to constant weight: 81.8 kg, 90% yield, mp 98-100° C.; 1H NMR (CDCl3) ∂ 0.96 (6H), 1.96 (1H), 2.70 (1H), 2.92 (1H), 3.15 (1H), 3.56 (1H), 3.90 (2H), 5.20 (1H), 7.70 (2H), 7.80 (2H). Anal. Calcd. for C16H18N2O3: C, 67.12; H, 6.34; N. 9.78. Found: C, 67.06; H, 6.20; N, 9.76. The crude product was collected by filtration washed with water (555.0 L) redissolved in toluene (500.0 L, 40° C.) The organic layer was washed with water (291.0 L) dried by azeotropic distillation (removing about 250 L of toluene) Heptane (300.0 L) was added the reaction was cooled at 0-5° C. for 3 h The product was collected by filtration washed with toluene/heptane (150.0 L, 1/2 ratio) The product was dried under vacuum at 55-60° C. to constant weight

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

実験手順: The compound was prepared according to Tanaka et al. Bull. Chem. Soc. Jpn. 1984, 57, 2184. A 0.05M solution of N-bromosuccinimide (724 mg, 4.07 mmol, 1.20 eq) in CH2Cl2 was added dropwise to a 0° C. solution of 4-(hydroxyiminomethyl)-benzonitrile (496 mg, 3.39 mmol, 1.00 eq) in CH2Cl2 (50 mL). The solution was warmed to room temperature before being volumetrically partitioned between two different reaction vials. Each vial was then concentrated and the crude residues were used without further purification. The compound was prepared before being volumetrically partitioned between two different reaction vials Each vial was then concentrated the crude residues were used without further purification

反応条件: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: The compound was prepared according to Biasotti et al. Bioorg. Med. Chem. 2003, 11, 2247. A suspension of 4-formylbenzonitrile (500 mg, 3.81 mmol, 1.00 eq), hydroxylamine hydrochloride (290 mg, 4.19 mmol, 1.10 eq), and sodium acetate (1.56 g, 19.05 mmol, 5.00 eq) in MeOH (50 mL) was heated at 70° C. for 4 h before concentration to dryness. The residue was then slurried in Et2O, filtered, and concentrated to afford the desired intermediate (496 mg, 3.39 mmol, 89%). The compound was prepared filtered concentrated

反応条件: temp:4.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of DMF (262.0 L), 4-cyanobenzaldoxime (46 kg, 342.1 mol), and N-chlorosuccinimide (54 kg, 389.4 mol) was added isobutyl vinylacetate (95 kg. 665.7 mol). The solution was cooled to 2-6° C., and triethylamine (40 kg. 388.6 mol) was slowly added over a period of 4 h. The reaction was stirred at the same temperature for an addition 1 h. Water (330.0 L) and hydrochloric acid (1 N, 49 L) were added. The crude product was collected by filtration, washed with water (555.0 L), and redissolved in toluene (500.0 L, 40° C.). The organic layer was washed with water (291.0 L) and dried by azeotropic distillation (removing about 250 L of toluene). Heptane (300.0 L) was added, and the reaction was cooled at 0-5° C. for 3 h. The product was collected by filtration and washed with toluene/heptane (150.0 L, 1/2 ratio). The product was dried under vacuum at 55-60° C. to constant weight: 81.8 kg, 90% yield, mp 98-100° C.; 1H NMR (CDCl3) ∂ 0.96 (6H), 1.96 (1H), 2.70 (1H), 2.92 (1H), 3.15 (1H), 3.56 (1H), 3.90 (2H), 5.20 (1H), 7.70 (2H), 7.80 (2H). Anal. Calcd. for C16H18N2O3: C, 67.12; H, 6.34; N. 9.78. Found: C, 67.06; H, 6.20; N, 9.76. The crude product was collected by filtration washed with water (555.0 L) redissolved in toluene (500.0 L, 40° C.) The organic layer was washed with water (291.0 L) dried by azeotropic distillation (removing about 250 L of toluene) Heptane (300.0 L) was added the reaction was cooled at 0-5° C. for 3 h The product was collected by filtration washed with toluene/heptane (150.0 L, 1/2 ratio) The product was dried under vacuum at 55-60° C. to constant weight

反応条件: temp:4.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of DMF (262.0 L), 4-cyanobenzaldoxime (46 kg, 342.1 mol), and N-chlorosuccinimide (54 kg, 389.4 mol) was added isobutyl vinylacetate (95 kg. 665.7 mol). The solution was cooled to 2-6° C., and triethylamine (40 kg. 388.6 mol) was slowly added over a period of 4 h. The reaction was stirred at the same temperature for an addition 1 h. Water (330.0 L) and hydrochloric acid (1 N, 49 L) were added. The crude product was collected by filtration, washed with water (555.0 L), and redissolved in toluene (500.0 L, 40° C.). The organic layer was washed with water (291.0 L) and dried by azeotropic distillation (removing about 250 L of toluene). Heptane (300.0 L) was added, and the reaction was cooled at 0-5° C. for 3 h. The product was collected by filtration and washed with toluene/heptane (150.0 L, 1/2 ratio). The product was dried under vacuum at 55-60° C. to constant weight: 81.8 kg, 90% yield, mp 98-100° C.; 1H NMR (CDCl3) ∂ 0.96 (6H), 1.96 (1H), 2.70 (1H), 2.92 (1H), 3.15 (1H), 3.56 (1H), 3.90 (2H), 5.20 (1H), 7.70 (2H), 7.80 (2H). Anal. Calcd. for C16H18N2O3: C, 67.12; H, 6.34; N. 9.78. Found: C, 67.06; H, 6.20; N, 9.76. The crude product was collected by filtration washed with water (555.0 L) redissolved in toluene (500.0 L, 40° C.) The organic layer was washed with water (291.0 L) dried by azeotropic distillation (removing about 250 L of toluene) Heptane (300.0 L) was added the reaction was cooled at 0-5° C. for 3 h The product was collected by filtration washed with toluene/heptane (150.0 L, 1/2 ratio) The product was dried under vacuum at 55-60° C. to constant weight

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: To a solution of 4-cyanobenzaldoxime (see Ex 2) (312 g, 2.13 mol) in tetrahydrofuran (3 L) at room temperature was added vinylacetic acid (552 g, 6.41 mol). The yellow solution was cooled in an ice bath and sodium hypochlorite solution (5200 mL)was added in a dropwise fashion over 2 h. After stirring overnight at room temperature the reaction was quenched with a 5% citric acid solution and diluted with 200 mL ether. The layers were separated and the aqueous acidified to pH 4 using citric acid. The acid layer was washed twice with 200 mL ether, the ether layers combined and extracted with saturated sodium bicarbonate solution. After acidifying the basic layer with citric acid, the product was extracted into 400 mL ether. The organic phase was washed three times with 150 mL water, once with brine, dried (MgSO4) and concentrated to give 220 g of 3-(4-cyanophenyl)isoxazolin-5-ylacetic acid as a white solid. Recrystallization from 25% water/ethanol yielded 165 g of analytically pure material; 1H NMR (300 MHz, CDCl3) δ 7.77-7.76 (d, J=1.8 Hz, 2H), 7.72-7.71 (d, J=1.8 Hz, 2H), 5.22-5.14 (m, 1H), 3.63-3.54 (dd, J=10.6 Hz, 16.8 Hz, 1H), 3.19-3.11 (dd, J=7.3 Hz, 16.8 Hz, 1H), 3.00-2.93 (dd, J=6.2 Hz, 16.5 Hz, 1H), 2.79-2.72 (dd, J=7.3 Hz, 16.5 Hz, 1H); IR (KBr): 3202, 2244, 1736, 1610, 1432, 1416, 1194, 1152, 928, 840, 562 cm-1. Anal. Calcd for C12H10N2O3 : C, 62.61; H, 4.38; N, 12.17. Found: C, 62.37; H, 4.47; N, 11.71. The yellow solution was cooled in an ice bath was quenched with a 5% citric acid solution diluted with 200 mL ether The layers were separated The acid layer was washed twice with 200 mL ether extracted with saturated sodium bicarbonate solution the product was extracted into 400 mL ether The organic phase was washed three times with 150 mL water once with brine, dried (MgSO4) concentrated

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

実験手順: To a solution of 4-cyanobenzaldoxime (see Ex 2) (312 g, 2.13 mol) in tetrahydrofuran (3 L) at room temperature was added vinylacetic acid (552 g, 6.41 mol). The yellow solution was cooled in an ice bath and sodium hypochlorite solution (5200 mL)was added in a dropwise fashion over 2 h. After stirring overnight at room temperature the reaction was quenched with a 5% citric acid solution and diluted with 200 mL ether. The layers were separated and the aqueous acidified to pH 4 using citric acid. The acid layer was washed twice with 200 mL ether, the ether layers combined and extracted with saturated sodium bicarbonate solution. After acidifying the basic layer with citric acid, the product was extracted into 400 mL ether. The organic phase was washed three times with 150 mL water, once with brine, dried (MgSO4) and concentrated to give 220 g of 3-(4-cyanophenyl)isoxazolin-5-ylacetic acid as a white solid. Recrystallization from 25% water/ethanol yielded 165 g of analytically pure material; 1H NMR (300 MHz, CDCl3) δ 7.77-7.76 (d, J=1.8 Hz, 2H), 7.72-7.71 (d, J=1.8 Hz, 2H), 5.22-5.14 (m, 1H), 3.63-3.54 (dd, J=10.6 Hz, 16.8 Hz, 1H), 3.19-3.11 (dd, J=7.3 Hz, 16.8 Hz, 1H), 3.00-2.93 (dd, J=6.2 Hz, 16.5 Hz, 1H), 2.79-2.72 (dd, J=7.3 Hz, 16.5 Hz, 1H); IR (KBr): 3202, 2244, 1736, 1610, 1432, 1416, 1194, 1152, 928, 840, 562 cm-1. Anal. Calcd for C12H10N2O3 : C, 62.61; H, 4.38; N, 12.17. Found: C, 62.37; H, 4.47; N, 11.71. The yellow solution was cooled in an ice bath was quenched with a 5% citric acid solution diluted with 200 mL ether The layers were separated The acid layer was washed twice with 200 mL ether extracted with saturated sodium bicarbonate solution the product was extracted into 400 mL ether The organic phase was washed three times with 150 mL water once with brine, dried (MgSO4) concentrated

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

実験手順: This material was prepared from 4-cyanobenzaldehyde according to Kawase and Kikugawa (J. Chem. Soc., Perkin Trans I 1979, 643). To a solution of 4-cyanobenzaldehyde (1.31 g, 10 mmol) in 1:1EtOH:pyridine (10 mL) was added hydroxylamine hydrochloride (0.70 g, 10 mmol). The resulting solution was stirred at room temperature for 18 h and was concentrated in vacuo to one-half volume. To this solution was added ice water, causing the product to crystallize from solution. Recrystallization from EtOH--water followed by drying over P2O5 afforded 1.46 g (100%) of the desired oxime; mp: 167.8-169.4° C. was concentrated in vacuo to one-half volume To this solution was added ice water to crystallize from solution Recrystallization from EtOH by drying over P2O5