반응 #2286324

반응 방정식

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

수율 36.0%

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

수율 36.0%

용매

acetic acid

ethyl acetate

acetic acid

반응 조건

후처리

1. 1
   온도was heated
2. 2
   온도to reflux for 2.5 h
3. 3
   온도heated
4. 4
   온도to reflux for 18 h
5. 5
   온도heated
6. 6
   온도to reflux for an additional 24 h
7. 7
   세척This solution was washed with a saturated aqueous sodium chloride solution (2×50 mL)
8. 8
   건조a saturated aqueous sodium carbonate solution (1×100 mL), dried with magnesium sulfate
9. 9
   여과filtered
10. 10
    농축concentrated 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
    온도was heated
13. 13
    온도to reflux for 3 d
14. 14
    온도At this time, the reaction was cooled to 25° C.
15. 15
    workup.ADDITIONdiluted with ethyl acetate (150 mL)
16. 16
    세척This solution was washed with a saturated aqueous sodium chloride solution (2×50 mL)
17. 17
    건조a saturated aqueous sodium carbonate solution (1×100 mL), dried with magnesium sulfate
18. 18
    여과filtered
19. 19
    농축concentrated under vacuum

실험 절차

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

출처