Reaktion #2286311

Reaktionsgleichung

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

Ausbeute 76.0%

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

Ausbeute 76.0%

Lösungsmittel

acetic acid

Reaktionsbedingungen

Aufarbeitung

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

Vorschrift

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

Quelle