反应 #2286292

反应方程式

acetic acid

sodium acetate

[3,5-dibromo-4-(6-chloro-5-isopropyl-pyridazin-3-yloxy)-phenyl]-acetic acid

→

[3,5-dibromo-4-(5-isopropyl-6-oxo-1,6-dihydro-pyridazin-3-yloxy)-phenyl]-acetic acid

收率 73.0%

[3,5-Dibromo-4-(5-isopropyl-6-oxo-1,6-dihydro-pyridazin-3-yloxy)-phenyl]-acetic acid

收率 73.0%

溶剂

toluene

反应条件

后处理

1. 1
   温度At this time, the reaction mixture was cooled to room temperature
2. 2
   浓缩concentrated under vacuum two times
3. 3
   workup.ADDITIONThe resulting residue was diluted with tetrahydrofuran (223 mL) and isopropyl acetate (892 mL)
4. 4
   洗涤was washed with water (3×150 mL)
5. 5
   其他The organic layer was separated
6. 6
   浓缩concentrated under vacuum to about 600 mL
7. 7
   workup.ADDITIONIsopropyl acetate (180 mL) was added
8. 8
   浓缩the mixture was concentrated under vacuum to about 450 mL
9. 9
   workup.ADDITIONHeptane (300 mL) was added in portions over 10 min
10. 10
    温度under reflux for 15 min
11. 11
    温度was cooled to room temperature
12. 12
    过滤The resulting solid was filtered
13. 13
    洗涤washed with 50% isopropyl acetate in heptane (200 mL)
14. 14
    其他dried under high vacuum overnight

实验过程

A solution of 2-[3,5-dibromo-4-(6-chloro-5-isopropyl-pyridazin-3-yloxy)-phenyl]-ethanol (12) (111.4 g, 247 mmol) in acetonitrile (223 mL), methylene chloride (343 mL) and sodium phosphate buffer (343 mL of a 0.67 M solution, pH=6.7) was treated with 2,2,6,6-tetramethyl-1-piperidinyloxy free group (2.35 g, 14.83 mmol) at room temperature. A solution of sodium chlorite (44.71 g, 395.5 mmol) in water (135 mL) and a solution of sodium hypochlorite (28 mL, 24.5 mmol) in water (50 mL) were then added simultaneously to the reaction mixture over 45 min. The temperature of the reaction mixture rose to 40° C. during the addition and a cold water bath was used to prevent the temperature from going any higher. The brown reaction mixture was stirred for 30 min. While cooling with cold water, a solution of sodium bisulfite (28.42 g, 297 mmol) in water (86 mL) was added dropwise to the reaction mixture over 5 min. The yellow solution was diluted with methylene chloride (223 mL) and extracted. The layers were separated and the organic layer was extracted with water (2×200 mL), dried with sodium sulfate, filtered and concentrated under vacuum to afford [3,5-dibromo-4-(6-chloro-5-isopropyl-pyridazin-3-yloxy)-phenyl]-acetic acid (13). Glacial acetic acid (549 mL) and sodium acetate (40.56 g, 494 mmol) were added to [3,5-dibromo-4-(6-chloro-5-isopropyl-pyridazin-3-yloxy)-phenyl]-acetic acid (13). The reaction mixture was heated to 120° C. for 24 h. At this time, the reaction mixture was cooled to room temperature, diluted with toluene (200 mL) and concentrated under vacuum two times. The resulting residue was diluted with tetrahydrofuran (223 mL) and isopropyl acetate (892 mL) and was washed with water (3×150 mL). The organic layer was separated and concentrated under vacuum to about 600 mL. Isopropyl acetate (180 mL) was added and the mixture was concentrated under vacuum to about 450 mL. Heptane (300 mL) was added in portions over 10 min. The mixture was stirred under reflux for 15 min and then was cooled to room temperature. The resulting solid was filtered, washed with 50% isopropyl acetate in heptane (200 mL), and dried under high vacuum overnight to afford [3,5-dibromo-4-(5-isopropyl-6-oxo-1,6-dihydro-pyridazin-3-yloxy)-phenyl]-acetic acid (14) (80.4 g, 73%) as a white solid; LRMS for C15H14Br2N2O4 (M+H) m/z=446. Molecular Weight=446.0978; Exact Mass=443.9320

来源