2,2,2-trichloro-1-ethoxyethanol

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

実験手順: Hydroxylamine hydrochloride (22.24 g, 320 mmol) in water (50 mL) was added to a suspension of 2,2,2-trichloro-1-ethoxyethanol (23.21 g, 120 mmol) and sodium sulfate (128 g, 900 mmol) in water (150 mL) and 2N HCl (100 mL). The mixture was stirred at 60° C. for 20 min. 3-Chloro-4-fluoroaniline (14.56 g, 100 mmol) in 2N HCl (100 mL) was added, and the mixture was heated to 90° C. for 2 h. The mixture was cooled to room temperature. The solid was collected by filtration, washed with water, and air dried to afford N-(3-chloro-4-fluorophenyl)-2-(hydroxyimino)ethanamide (19.45 g, 90% yield). This material was used in the next step without further purification. the mixture was heated to 90° C. for 2 h The mixture was cooled to room temperature The solid was collected by filtration washed with water, and air dried

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

実験手順: Hydroxylamine hydrochloride (22.24 g, 320 mmol) in water (50 mL) was added to a suspension of 2,2,2-trichloro-1-ethoxyethanol (23.21 g, 120 mmol) and sodium sulfate (128 g, 900 mmol) in water (150 mL) and 2N HCl (100 mL). The mixture was stirred at 60° C. for 20 min. 3-Chloro-4-fluoroaniline (14.56 g, 100 mmol) in 2N HCl (100 mL) was added, and the mixture was heated to 90° C. for 2 h. The mixture was cooled to room temperature. The solid was collected by filtration, washed with water, and air dried to afford N-(3-chloro-4-fluorophenyl)-2-(hydroxyimino)ethanamide (19.45 g, 90% yield). This material was used in the next step without further purification. the mixture was heated to 90° C. for 2 h The mixture was cooled to room temperature The solid was collected by filtration washed with water, and air dried

反応条件: temp:40.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Flask A: A 2 L 3-neck flask with a temperature probe adapter was fixed with a mechanical stirrer, condenser, and temperature probe; the flask was charged with hydroxylamine hydrochloride (Fluka; 12.47 g, 179 mmol), Na2SO4 (51.7 g, 364 mmol), 2,2,2-trichloro-1-ethoxyethanol (15.78 g, 82 mmol), and water (240 ml). This was stirred to 40° C. to affect dissolution. Flask B: A mixture of 2-bromo-3-fluoroaniline (10.33 g, 54.4 mmol) in water (32.0 mL)/conc. HCl (14.95 mL, 179 mmol) was stirred at RT and then at 50° C. to attempt dissolution; EtOH (10 mL) was added as another attempt to dissolve the aniline to no avail. The fine slurry was added to Flask A containing the stirring 2,2,2-trichloro-1-ethoxyethanol solution at 40° C. The reaction was heated to 100° C. and was stirred for 1 h. The reaction was cooled to 5° C. in an ice bath, filtered through a disposable 0.45 micron ZapCap filter (very slow filtration), and washed with water to give N-(2-bromo-3-fluorophenyl)-2-(hydroxyimino)acetamide (12.34 g, 47.3 mmol, 87% yield) as a brown solid after it was dried in a vacuum oven. 1H NMR (400 MHz, CDCl3) δ ppm 6.92 (td, J=8.31, 1.37 Hz, 1H), 7.32 (td, J=8.31, 6.26 Hz, 1H), 7.60 (s, 1H), 7.87 (s, 1H), 8.25 (d, J=8.41 Hz, 1H), 8.98 (br. s., 1H). 19F NMR (377 MHz, CDCl3) δ ppm −104.01 (s, 1F). MS (ESI, pos. ion) m/z: 260.9/262.9 (M+1). Flask A: A 2 L 3-neck flask with a temperature probe adapter was fixed with a mechanical stirrer, condenser dissolution at 50° C. dissolution The reaction was heated to 100° C. was stirred for 1 h The reaction was cooled to 5° C. in an ice bath filtered through a disposable 0.45 micron ZapCap filter ( very slow filtration), and washed with water

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

実験手順: Hydroxylamine hydrochloride (6.67 g, 96 mmol) in water (15 mL) was added to a suspension of 2,2,2-trichloro-1-ethoxyethanol (6.96 g, 36 mmol) and sodium sulfate (38.3 g, 270 mmol) in water (45 mL) and 2N HCl (30 mL). The mixture was stirred at 60° C. for 20 min. 4-Bromo-2-methoxybenzenamine (6.06 g, 30 mol) in 2N HCl (30 mL) was added, and the mixture was heated to 90° C. for 2 h. The mixture was cooled to room temperature. The solid was collected by filtration, washed with water, and air dried to afford the title compound (5.55 g, crude, 68% yield). This material was used in the next step without further purification. MS (ESI) m/e [M+1]+ 273, 275. the mixture was heated to 90° C. for 2 h The mixture was cooled to room temperature The solid was collected by filtration washed with water, and air dried

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

実験手順: Hydroxylamine hydrochloride (6.67 g, 96 mmol) in water (15 mL) was added to a suspension of 2,2,2-trichloro-1-ethoxyethanol (6.96 g, 36 mmol) and sodium sulfate (38.3 g, 270 mmol) in water (45 mL) and 2N HCl (30 mL). The mixture was stirred at 60° C. for 20 min. 4-Bromo-2-methoxybenzenamine (6.06 g, 30 mol) in 2N HCl (30 mL) was added, and the mixture was heated to 90° C. for 2 h. The mixture was cooled to room temperature. The solid was collected by filtration, washed with water, and air dried to afford the title compound (5.55 g, crude, 68% yield). This material was used in the next step without further purification. MS (ESI) m/e [M+1]+ 273, 275. the mixture was heated to 90° C. for 2 h The mixture was cooled to room temperature The solid was collected by filtration washed with water, and air dried

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

実験手順: A solution containing NH2OH.HCl (3.2 g, 46 mmol), anhydrous sodium sulphate (13 g, 93 mmol), and 2.2.2-trichloro-1-ethoxy ethanol (4.1 g, 21.2 mmol) in water (60 mL) was added to a solution of 2-chloro-4-fluroaniline (2 g, 0.27 mmol) in 4 M HCl (25 mL). The solution was refluxed for 40 minutes forming a white precipitate in the process. The mixture was cooled to room temperature, extracted with ethyl acetate three times, dried over sodium sulfate, filtered and concentrated in vacuo to provide 2.01 g of N-(2-chloro-4-fluoro-phenyl)-2-((E)-hydroxyimino)-acetamide: 1H NMR (300 MHz, CDCl3) δ 8.8 (bs, 1H), 8.4 (dd, 1H), 7.9 (s, 1H), 7.6 (s, 1H), 7.2 (dd, 1H), 7.0 (ddd, 1H). The solution was refluxed for 40 minutes forming a white precipitate in the process extracted with ethyl acetate three times dried over sodium sulfate filtered concentrated in vacuo

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

実験手順: Chloral alcoholate (0.43 g, 1.05 eq) and Na2SO4 (2.84 g, 20 mmol) were dissolved in 10 mL water. 3-Bromo-2-methylaniline (0.33 g, 1.77 mmol)was added to the solution followed by 0.16 mL conc. HCl aqueous solution and NH2OH.HCl (0.38 g, 3.0 eq). The mixture was refluxed for 15 min and stirring was continued for additional 1 hr at RT. The precipitate was collected by filtration, washed with water and dried under vacuum. This precipitate was dissolved in 1 mL H2SO4 and the solution was heated (80° C.) for 15 min. After cooling down to RT, the mixture was poured into ice-water mixture and the precipitate was collected, washed with water and dried under vacuum to give the title compound (0.26 g, 61%). The mixture was refluxed for 15 min The precipitate was collected by filtration washed with water dried under vacuum This precipitate was dissolved in 1 mL H2SO4 After cooling down to RT the mixture was poured into ice-water mixture the precipitate was collected washed with water dried under vacuum

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

実験手順: Chloral alcoholate (0.43 g, 1.05 eq) and Na2SO4(2.84 g, 20 mmol) were dissolved in 10 mL water. 3-Bromo-2-methylaniline (0.33 g, 1.77 mmol) was added to the solution followed by 0.16 mL conc. HCl aqueous solution and NH2OH.HCl (0.38 g, 3.0 eq). The mixture was refluxed for 15 min and stirring was continued for additional 1 hr at RT. The precipitate was collected by filtration, washed with water and dried under vacuum. This precipitate was dissolved in 1 mL H2SO4 and the solution was heated (80° C.) for 15 min. After cooling down to RT, the mixture was poured into ice-water mixture and the precipitate was collected, washed with water and dried under vacuum to give the title compound (0.26 g, 61%). The mixture was refluxed for 15 min The precipitate was collected by filtration washed with water dried under vacuum This precipitate was dissolved in 1 mL H2SO4 After cooling down to RT the mixture was poured into ice-water mixture the precipitate was collected washed with water dried under vacuum

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

実験手順: Hydroxylamine hydrochloride (22.24 g, 320 mmol) in water (50 mL) was added to a suspension of 2,2,2-trichloro-1-ethoxyethanol (23.21 g, 120 mmol) and sodium sulfate (128 g, 900 mmol) in water (150 mL) and 2N HCl (100 mL). The mixture was stirred at 60° C. for 20 min. 3-Chloro-4-fluoroaniline (14.56 g, 100 mmol) in 2N HCl (100 mL) was added, and the mixture was heated to 90° C. for 2 h. The mixture was cooled to room temperature. The solid was collected by filtration, washed with water, and air dried to afford N-(3-chloro-4-fluorophenyl)-2-(hydroxyimino)ethanamide (19.45 g, 90% yield). This material was used in the next step without further purification. the mixture was heated to 90° C. for 2 h The mixture was cooled to room temperature The solid was collected by filtration washed with water, and air dried

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

実験手順: Chloral alcoholate (0.43 g, 1.05 eq) and Na2SO4 (2.84 g, 20 mmol) were dissolved in 10 mL water. 3-Bromo-2-methylaniline (0.33 g, 1.77 mmol) was added to the solution followed by 0.16 mL conc. HCl aqueous solution and NH2OH.HCl (0.38 g, 3.0 eq). The mixture was refluxed for 15 min and stirring was continued for additional 1 hr at RT. The precipitate was collected by filtration, washed with water and dried under vacuum. This precipitate was dissolved in 1 mL H2SO4 and the solution was heated (80° C.) for 15 min. After cooling down to RT, the mixture was poured into ice-water mixture and the precipitate was collected, washed with water and dried under vacuum to give the title compound (0.26 g, 61%). The mixture was refluxed for 15 min The precipitate was collected by filtration washed with water dried under vacuum This precipitate was dissolved in 1 mL H2SO4 After cooling down to RT the mixture was poured into ice-water mixture the precipitate was collected washed with water dried under vacuum

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

実験手順: Chloral alcoholate (0.43 g, 1.05 eq) and Na2SO4 (2.84 g, 20 mmol) were dissolved in 10 mL water. 3-Bromo-2-methylaniline (0.33 g, 1.77 mmol) was added to the solution followed by 0.16 mL conc. HCl aqueous solution and NH2OH.HCl (0.38 g, 3.0 eq). The mixture was refluxed for 15 min and stirring was continued for additional 1 hr at RT. The precipitate was collected by filtration, washed with water and dried under vacuum. This precipitate was dissolved in 1 mL H2SO4 and the solution was heated (80° C.) for 15 min. After cooling down to RT, the mixture was poured into ice-water mixture and the precipitate was collected, washed with water and dried under vacuum to give the title compound (0.26 g, 61%). The mixture was refluxed for 15 min The precipitate was collected by filtration washed with water dried under vacuum This precipitate was dissolved in 1 mL H2SO4 After cooling down to RT the mixture was poured into ice-water mixture the precipitate was collected washed with water dried under vacuum

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

実験手順: A solution containing NH2OH.HCl (3.2 g, 46 mmol), anhydrous sodium sulphate (13 g, 93 mmol), and 2.2.2-trichloro-1-ethoxy ethanol (4.1 g, 21.2 mmol) in water (60 mL) was added to a solution of 2-chloro-4-fluoroaniline (2 g, 0.27 mmol) in 4 M HCl (25 mL). The solution was refluxed for 40 minutes forming a white precipitate in the process. The mixture was cooled to room temperature, extracted with ethyl acetate three times, dried over sodium sulfate, filtered and concentrated in vacuo to provide 2.01 g of N-(2-chloro-4-fluoro-phenyl)-2-((E)-hydroxyimino)-acetamide: 1H NMR (300 MHz, CDCl3) δ 8.8 (bs, 1H), 8.4 (dd, 1H), 7.9 (s, 1H), 7.6 (s, 1H), 7.2 (dd, 1H), 7.0 (ddd, 1H). The solution was refluxed for 40 minutes forming a white precipitate in the process extracted with ethyl acetate three times dried over sodium sulfate filtered concentrated in vacuo