反応 #2286324

反応方程式

hydrochloric acid

hydrochloric acid

(6-chloro-5-isopropyl-pyridazin-3-yl)-[2,6-dibromo-4-(tetrahydro-pyran-2-yloxymethyl)-phenyl]-acetonitrile

sodium acetate

→

6-(2,6-dibromo-4-chloromethyl-benzyl)-4-isopropyl-pyridazin-3-one

収率 36.0%

6-(2,6-Dibromo-4-chloromethyl-benzyl)-4-isopropyl-pyridazin-3-one

収率 36.0%

溶媒

acetic acid

ethyl acetate

acetic acid

反応条件

後処理

1. 1
   温度was heated
2. 2
   温度to reflux for 2.5 h
3. 3
   温度heated
4. 4
   温度to reflux for 18 h
5. 5
   温度heated
6. 6
   温度to reflux for an additional 24 h
7. 7
   洗浄This solution was washed with a saturated aqueous sodium chloride solution (2×50 mL)
8. 8
   乾燥a saturated aqueous sodium carbonate solution (1×100 mL), dried with magnesium sulfate
9. 9
   ろ過filtered
10. 10
    濃縮concentrated under vacuum
11. 11
    workup.ADDITIONThe resulting brown oil was treated with glacial acetic acid (1.0 mL) and concentrated hydrochloric acid (6.0 mL)
12. 12
    温度was heated
13. 13
    温度to reflux for 3 d
14. 14
    温度At this time, the reaction was cooled to 25° C.
15. 15
    workup.ADDITIONdiluted with ethyl acetate (150 mL)
16. 16
    洗浄This solution was washed with a saturated aqueous sodium chloride solution (2×50 mL)
17. 17
    乾燥a saturated aqueous sodium carbonate solution (1×100 mL), dried with magnesium sulfate
18. 18
    ろ過filtered
19. 19
    濃縮concentrated under vacuum

実験手順

A mixture of (6-chloro-5-isopropyl-pyridazin-3-yl)-[2,6-dibromo-4-(tetrahydro-pyran-2-yloxymethyl)-phenyl]-acetonitrile (61) (332.8 mg, 0.61 mmol) and sodium acetate (103.8 mg, 1.26 mmol) in glacial acetic acid (2.7 mL) was heated to reflux for 2.5 h. The reaction was then treated with concentrated hydrochloric acid (2.0 mL) and heated to reflux for 18 h. At this time, the reaction was treated with more concentrated hydrochloric acid (6.0 mL) and additional glacial acetic acid (3.0 mL) and heated to reflux for an additional 24 h. The reaction was then cooled to 25° C. and diluted with ethyl acetate (150 mL). This solution was washed with a saturated aqueous sodium chloride solution (2×50 mL) and a saturated aqueous sodium carbonate solution (1×100 mL), dried with magnesium sulfate, filtered, and concentrated under vacuum. The resulting brown oil was treated with glacial acetic acid (1.0 mL) and concentrated hydrochloric acid (6.0 mL) and was heated to reflux for 3 d. At this time, the reaction was cooled to 25° C. and diluted with ethyl acetate (150 mL). This solution was washed with a saturated aqueous sodium chloride solution (2×50 mL) and a saturated aqueous sodium carbonate solution (1×100 mL), dried with magnesium sulfate, filtered, and concentrated under vacuum. Flash chromatography (Merck Silica gel 60, 230-400 mesh, 2/1 hexanes/ethyl acetate) afforded 6-(2,6-dibromo-4-chloromethyl-benzyl)-4-isopropyl-pyridazin-3-one (62) (96.3 mg, 36%) as an off-white solid; LRMS for C15H15Br2ClN2O (M+H) at m/z=433. Molecular Weight=434.5606; Exact Mass=431.9240

出典