反应 #2286304

反应方程式

methyl iodide

acetic acid 2-[3,5-dichloro-4-(5-isopropyl-6-oxo-1,6-dihydro-pyridazin-3-yloxy)-phenyl]-ethyl ester

Acetic acid 2-[3,5-dichloro-4-(5-isopropyl-6-oxo-1,6-dihydro-pyridazin-3-yloxy)-phenyl]-ethyl ester

potassium carbonate

methyl iodide

potassium carbonate

→

2-[3,5-dichloro-4-(5-isopropyl-1-methyl-6-oxo-1,6-dihydro-pyridazin-3-yloxy)-phenyl]ethyl ester

收率 72.0%

acetic acid 2-[3,5-dichloro-4-(5-isopropyl-1-methyl-6-oxo-1,6-dihydro-pyridazin-3-yloxy)-phenyl]-ethyl ester

收率 72.0%

反应条件

后处理

1. 1
   温度The mixture was heated at 40° C. for 2 h
2. 2
   浓缩The reaction mixture was concentrated
3. 3
   其他the resulting residue was partitioned between ethyl acetate (50 mL) and water (25 mL)
4. 4
   萃取The water layer was re-extracted with ethyl acetate (25 mL)
5. 5
   干燥dried with sodium sulfate
6. 6
   过滤filtered
7. 7
   浓缩concentrated
8. 8
   workup.DISSOLUTIONThe resulting residue was dissolved in 25% ethyl acetate in hexanes
9. 9
   其他was purified by flash chromatography (Biotage 40S)
10. 10
    洗涤eluted with 25-50% ethyl acetate in hexanes
11. 11
    其他The desired fractions were collected
12. 12
    浓缩concentrated under vacuum
13. 13
    其他The resulting solid was dried under high vacuum

实验过程

A mixture of acetic acid 2-[3,5-dichloro-4-(5-isopropyl-6-oxo-1,6-dihydro-pyridazin-3-yloxy)-phenyl]-ethyl ester (34) (531 mg, 1.38 mmol), potassium carbonate (280 mg, 2.03 mmol) and methyl iodide (2 mL, 32.1 mmol) was warmed to 40° C. for 2 h. Additional methyl iodide was added (1 mL, 16.05 mmol) followed by potassium carbonate (140 mg, 1.01 mmol). The mixture was heated at 40° C. for 2 h and then was stirred at room temperature for 24 h. The reaction mixture was concentrated and the resulting residue was partitioned between ethyl acetate (50 mL) and water (25 mL). The water layer was re-extracted with ethyl acetate (25 mL). The organic layers were combined, dried with sodium sulfate, filtered, and concentrated. The resulting residue was dissolved in 25% ethyl acetate in hexanes and was purified by flash chromatography (Biotage 40S) using silica gel eluted with 25-50% ethyl acetate in hexanes. The desired fractions were collected and concentrated under vacuum. The resulting solid was dried under high vacuum to afford 2-[3,5-dichloro-4-(5-isopropyl-1-methyl-6-oxo-1,6-dihydro-pyridazin-3-yloxy)-phenyl]ethyl ester (35) (395 mg, 72%) as a clear oil; LRMS for C18H20Cl2N2O4 (M+) m/z=399. Molecular Weight=399.2771; Exact Mass=398.0800

来源