反応 #2286311

反応方程式

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

収率 76.0%

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

収率 76.0%

溶媒

acetic acid

反応条件

後処理

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

実験手順

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

出典