반응 #2286311

반응 방정식

sodium hydroxide

(4-amino-2,6-dichloro-phenyl)-(6-chloro-5-isopropyl-pyridazin-3-yl)-acetonitrile

(4-Amino-2,6-dichloro-phenyl)-(6-chloro-5-isopropyl-pyridazin-3-yl)-acetonitrile

water

hydrochloric acid

→

6-(4-amino-2,6-dichloro-benzyl)-4-isopropyl-pyridazin-3-one

수율 76.0%

6-(4-Amino-2,6-dichloro-benzyl)-4-isopropyl-pyridazin-3-one

수율 76.0%

용매

acetic acid

반응 조건

후처리

1. 1
   온도At this time, the reaction was cooled to room temperature
2. 2
   workup.ADDITIONthe mixture was poured onto water (250 mL)
3. 3
   여과The resulting solids were filtered
4. 4
   세척washed with water and petroleum ether
5. 5
   기타The solids were collected
6. 6
   workup.DISSOLUTIONdissolved in hot ethyl acetate
7. 7
   workup.ADDITIONSilica gel 60 (70-230 mesh) was added
8. 8
   농축the solvent was concentrated under vacuum
9. 9
   기타The resulting mixture was purified by flash chromatography (Biotage 75S)
10. 10
    세척eluted with 40% ethyl acetate in hexanes to 50% ethyl acetate in hexanes containing 0.5% glacial acetic acid
11. 11
    기타The desired fractions were collected
12. 12
    농축concentrated under vacuum
13. 13
    기타to afford a solid which
14. 14
    기타was dried under high vacuum

실험 절차

A mixture of (4-amino-2,6-dichloro-phenyl)-(6-chloro-5-isopropyl-pyridazin-3-yl)-acetonitrile (45) (6.98 g, 19.63 mmol), water (30 mL), concentrated hydrochloric acid (120 mL) and glacial acetic acid (30 mL) was heated to 120° C. for 24 h. At this time, the reaction was cooled to room temperature and the mixture was poured onto water (250 mL). The pH was made neutral (pH=7) by the addition of a 4N aqueous sodium hydroxide solution. The suspension was placed in the freezer for 15 min. The resulting solids were filtered and washed with water and petroleum ether. The solids were collected and dissolved in hot ethyl acetate. Silica gel 60 (70-230 mesh) was added and the solvent was concentrated under vacuum. The resulting mixture was purified by flash chromatography (Biotage 75S) using silica gel eluted with 40% ethyl acetate in hexanes to 50% ethyl acetate in hexanes containing 0.5% glacial acetic acid. The desired fractions were collected and concentrated under vacuum to afford a solid which was dried under high vacuum to afford 6-(4-amino-2,6-dichloro-benzyl)-4-isopropyl-pyridazin-3-one (46) (4.65 g, 76%) as an off-white solid; LRMS for C14H15Cl2N3O (M+H) m/z=312. Molecular Weight=312.2012; Exact Mass=311.0592

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