oxalyl dibromide

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:

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 (2Z)-3-[2,6-dibromo-4-(methoxycarbonyl)phenyl]prop-2-enoic acid (1.24 g) (contaminated with 20% of the E isomer) in dichloromethane (34 mL) at 0° C. under nitrogen atmosphere was added oxalyl bromide (2 mL of a 2M solution in dichloromethane) followed by dimethylformamide (170 μL). The mixture was then warmed to rt and stirred until all gas evolution had ceased. The reaction was cooled again to 0° C. where diisopropylethylamine (83 μL) and 2,6-dichloroaniline (607 mg) were added and the reaction warmed to rt and stirred for 16 h. The reaction mixture was then poured into brine and extracted into ethyl acetate. A small amount of unreacted starting acid was removed by washing the organic layer with saturated sodium bicarbonate solution, before drying over MgSO4 and concentrating. The residue was purified by column chromatography on silica gel to give the title compound still contaminated with 20% of the E isomer. 1H NMR (500 MHz, CDCl3): δ 8.99 (br.s, 1H, Z isomer); 8.26 (br.s, 1H, E isomer); 8.20 (s, 1H, Z isomer); 7.80-6.40 (m, 6H); 3.96 (s, 3H, E isomer); 3.92 (s, 3H, Z isomer). Mass spectrum: m/z 507 (M+H). at 0° C. were added the reaction warmed to rt stirred for 16 h extracted into ethyl acetate was removed by washing the organic layer with saturated sodium bicarbonate solution before drying over MgSO4 concentrating The residue was purified by column chromatography on silica gel

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

実験手順: To a −78° C. solution of 11.56 g of 3-(2,6-dibromo-4-methoxyphenyl)-propionic acid in 300 mL of CH2Cl2 was added dropwise 17.1 mL of a 1.0M solution of oxalyl bromide, then 1.7 mL of DMF. The mixture was allowed to warm to room temperature. When gas evolution ceased, the mixture was recooled to −78° C. Diisopropyl ethylamine (7.14 mL) was added dropwise, then a solution of 5.54 g of 2,6-dichloroaniline in 10 mL of CH2Cl2 was added dropwise. The mixture was allowed to warm to room temperature, then stirred overnight at this temperature. The white precipitate was collected to yield the N-(2,6-Dichlorophenyl)-3-(2,6-dibromo-4-methoxyphenyl)-propionamide as a white solid. The filtrate was concentrated and recrystallized from EtOH to yield an additional amount of N-(2,6-Dichlorophenyl)-3-(2,6-dibromo-4-methoxyphenyl)-propionamide as a white solid. Mass spectrum (ESI) 481.9 (M+1). 1H NMR (500 MHz, DMSO-d6): δ 9.89 (s, 1H); 7.53 (d, J=8.2 Hz, 2H); 7.34 (t, J=8.0 Hz, 1H); 7.27 (s, 2H); 3.77 (s, 3H); 3.16 (m, 2H); 2.53 (m, 2H). was recooled to −78° C to warm to room temperature The white precipitate was collected

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-hydroxy-5, 5-dimethyl-5H-furan-2-one (2.1 g, 16.4 mmol) in DCE (40 mL) and DMF (1.5 mL) at 0° C. was added dropwise oxalyl bromide (3.0 mL, 32 mmol, 2 equiv). The mixture was stirred at room temperature for 4-5 h, and then put in an ice bath. Ice water (100 mL) was added slowly. The mixture was extracted with CH2Cl2 (100 mL). The organic phase was washed with 10% NaHCO3 and again with water, dried over sodium sulfate and evaporated to give the title compound 2.7 g (86% yield). put in an ice bath The mixture was extracted with CH2Cl2 (100 mL) The organic phase was washed with 10% NaHCO3 and again with water dried over sodium sulfate evaporated

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

実験手順: A suspension of methyl 4-chloro-3-(2,3-dioxo-3,4-dihydropyrazin-1(2H)-yl)benzoate (Example 330d, 8 g) in DCM (80 mL) was treated with N,N-dimethylformamide (0.220 mL) and oxalyl bromide (2.94 mL) dropwise over 5 min at room temperature under nitrogen. The resulting mixture was stirred at 20° C. for 16 h. The reaction mixture turned black and was evaporated to afford crude product. Purification (SiO2 chromatography eluting with 30% diethyl ether in dichloromethane) gave the subtitle compound (6.33 g). was evaporated to afford crude product Purification (SiO2 chromatography eluting with 30% diethyl ether in dichloromethane)

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-hydroxy-5,5-dimethyl-5H-furan-2-one (2.1 g, 16.4 mmol) in DCE (40 mL) and DMF (1.5 mL) at 0° C. was added dropwise oxalyl bromide (3.0 mL, 32 mmol, 2 equiv). The mixture was stirred at room temperature for 4-5 h, and then put in an ice bath. Ice water (100 mL) was added slowly. The mixture was extracted with CH2Cl2 (100 mL). The organic phase was washed with 10% NaHCO3 and again with water, dried over sodium sulfate and evaporated to give the title compound 2.7 g (86% yield). put in an ice bath The mixture was extracted with CH2Cl2 (100 mL) The organic phase was washed with 10% NaHCO3 and again with water dried over sodium sulfate evaporated

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 round bottom flask containing 2-bromo-5-pyridinecarboxylic acid (10.0 g, 49 mmol) in DCM (500 mL) was added oxalyl bromide (7.4 mL) and 5 drops of DMF. After some gas evolution, the reaction mixture was stirred at reflux ca 6 h, then cooled to rt and heptane 100 mL was added, followed by concentration of the mixture. The mixture was then suspended in THF 400 mL, cooled to 0° C. t-BuOK (5.8 g, 52 mmol) was then added and the r×n allowed to warm to rt and stirred for 2 h. The mixture poured into EtOAc, washed with 1 N NaOH, water, brine, dried MgSO4 filtered and concentrated. The residue was purified by silica gel chromatography Biotage 40S Heptane EtOAc 0-80% 3 L to afford the title compound 4.2 g (36%) of as a white solid. 1H NMR (400 MHz, DMSO-d6) □ ppm 8.78-8.86 (1H, m), 8.14 (1H, dd, J=8.4, 2.4 Hz), 7.81 (1H d, J=8.4 Hz), 1.56 (9H, s). at reflux ca 6 h was then added to warm to rt stirred for 2 h washed with 1 N NaOH, water, brine, dried MgSO4 filtered concentrated The residue was purified by silica gel chromatography Biotage 40S Heptane EtOAc 0-80% 3 L

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

実験手順: To a round bottom flask containing 2-bromo-5-pyridinecarboxylic acid (10.0 g, 49 mmol) in DCM (500 mL) was added oxalyl bromide (7.4 mL) and 5 drops of DMF. After some gas evolution, the reaction mixture was stirred at reflux ca 6 h, then cooled to rt and heptane 100 mL was added, followed by concentration of the mixture. The mixture was then suspended in THF 400 mL, cooled to 0° C. t-BuOK (5.8 g, 52 mmol) was then added and the r×n allowed to warm to rt and stirred for 2 h. The mixture poured into EtOAc, washed with 1 N NaOH, water, brine, dried MgSO4 filtered and concentrated. The residue was purified by silica gel chromatography Biotage 40S Heptane EtOAc 0-80% 3 L to afford the title compound 4.2 g (36%) of as a white solid. 1H NMR (400 MHz, DMSO-d6) □ ppm 8.78-8.86 (1H, m), 8.14 (1H, dd, J=8.4, 2.4 Hz), 7.81 (1H d, J=8.4 Hz), 1.56 (9H, s). at reflux ca 6 h was then added to warm to rt stirred for 2 h washed with 1 N NaOH, water, brine, dried MgSO4 filtered concentrated The residue was purified by silica gel chromatography Biotage 40S Heptane EtOAc 0-80% 3 L