反応 #2286298

反応方程式

sodium acetate

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

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

→

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

収率 72.0%

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

収率 72.0%

溶媒

acetic acid

反応条件

後処理

1. 1
   温度The reaction mixture was cooled to room temperature
2. 2
   濃縮concentrated
3. 3
   workup.ADDITIONThe resulting residue was diluted with water (200 mL)
4. 4
   workup.ADDITIONwas made basic to pH=9 by the addition of a 1N aqueous sodium hydroxide solution
5. 5
   抽出This solution was extracted with ethyl acetate (1×100 mL)
6. 6
   workup.ADDITIONThe water layer was acidified to pH=3 by the addition of a 1N aqueous hydrochloric acid solution
7. 7
   抽出The water layer was extracted with ethyl acetate (3×100 mL)
8. 8
   乾燥dried with sodium sulfate
9. 9
   ろ過filtered
10. 10
    濃縮concentrated under vacuum
11. 11
    workup.ADDITIONHeptane (20 mL) was added to this mixture
12. 12
    濃縮The solvents were then concentrated under vacuum to a volume of approximately 20 mL
13. 13
    ろ過The solids were filtered
14. 14
    洗浄washed with a 1:1 ethyl acetate
15. 15
    その他The solid was dried under high vacuum

実験手順

A mixture of glacial acetic acid (16.7 mL), sodium acetate (480 mg, 5.85 mmol) and [3,5-dibromo-4-(6-chloro-5-isopropyl-pyridazin-3-yloxy)-phenyl]-proprionic acid (22) (800 mg, 1.67 mmol) was heated to 120° C. for 24 h. The reaction mixture was cooled to room temperature and concentrated. The resulting residue was diluted with water (200 mL) and was made basic to pH=9 by the addition of a 1N aqueous sodium hydroxide solution. This solution was extracted with ethyl acetate (1×100 mL) and the ethyl acetate was discarded. The water layer was acidified to pH=3 by the addition of a 1N aqueous hydrochloric acid solution. The water layer was extracted with ethyl acetate (3×100 mL). The organic layers were combined, dried with sodium sulfate, filtered and concentrated under vacuum. The resulting solid was slurried in ethyl acetate (20 mL). Heptane (20 mL) was added to this mixture. The solvents were then concentrated under vacuum to a volume of approximately 20 mL. The solids were filtered and washed with a 1:1 ethyl acetate:heptane solution (2×10 mL). The solid was dried under high vacuum to afford [3,5-dibromo-4-(5-isopropyl-6-oxo-1,6-dihydro-pyridazin-3-yloxy)-phenyl]-proprionic acid (23) (553 mg, 72%) as an off-white solid; LRMS for C16H16Br2N2O4 (M+H) m/z=461. Molecular Weight=460.1249; Exact Mass=457.9477

出典