反应 #2286318

ord-6a7de175e06d4513bf59eee6c17ef0ff

反应方程式

CC(C)c1cc(Cc2c(Cl)cc(CC#N)cc2Cl)n[nH]c1=O
[3,5-dichloro-4-(5-isopropyl-6-oxo-1,6-dihydro-pyridazin-3-ylmethyl)-phenyl]-acetonitrile
CC(C)c1cc(Cc2c(Cl)cc(CC#N)cc2Cl)n[nH]c1=O
[3,5-Dichloro-4-(5-isopropyl-6-oxo-1,6-dihydro-pyridazin-3-ylmethyl)-phenyl]-acetonitrile
CCOC(C)=O
ethyl acetate
CC(C)c1cc(Cc2c(Cl)cc(CC(=O)O)cc2Cl)n[nH]c1=O
acetic acid
收率 13.0%
CC(C)c1cc(Cc2c(Cl)cc(CC(=O)O)cc2Cl)n[nH]c1=O
[3,5-Dichloro-4-(5-isopropyl-6-oxo-1,6-dihydro-pyridazin-3-ylmethyl)-phenyl]-acetic acid
收率 13.0%

反应条件

详细条件
See reaction.notes.procedure_details.

后处理

  1. 1
    温度was heated
  2. 2
    温度to reflux for 24 h
  3. 3
    洗涤washed with a saturated aqueous sodium chloride solution (20 mL) and water (10 mL)
  4. 4
    萃取extracted with ethyl acetate (50 mL)
  5. 5
    干燥dried over magnesium sulfate
  6. 6
    过滤filtered
  7. 7
    浓缩concentrated under vacuum
  8. 8
    其他The resulting oil was purified by HPLC (acetonitrile/water with 0.1% trifluoroacetic acid)
  9. 9
    其他The desired fractions were collected
  10. 10
    浓缩concentrated
  11. 11
    其他freeze dried
  12. 12
    其他The resulting solid was purified by flash chromatography
  13. 13
    洗涤eluted with 10% methanol in methylene chloride
  14. 14
    其他The desired fractions were collected
  15. 15
    浓缩concentrated under vacuum
  16. 16
    其他to afford a solid which
  17. 17
    其他was dried under high vacuum

实验过程

A mixture of [3,5-dichloro-4-(5-isopropyl-6-oxo-1,6-dihydro-pyridazin-3-ylmethyl)-phenyl]-acetonitrile (55) (assume 0.180 mmol) in concentrated hydrochloric acid (4 mL) was heated to reflux for 24 h. The reaction mixture was cooled to room temperature, diluted with ethyl acetate (75 mL) and washed with a saturated aqueous sodium chloride solution (20 mL) and water (10 mL). The water layers were combined and extracted with ethyl acetate (50 mL). The organic layers were combined, dried over magnesium sulfate, filtered, and concentrated under vacuum. The resulting oil was purified by HPLC (acetonitrile/water with 0.1% trifluoroacetic acid). The desired fractions were collected, concentrated and freeze dried. The resulting solid was purified by flash chromatography using silica gel eluted with 10% methanol in methylene chloride. The desired fractions were collected and concentrated under vacuum to afford a solid which was dried under high vacuum to afford 3,5-dichloro-4-(5-isopropyl-6-oxo-1,6-dihydro-pyridazin-3-ylmethyl)-phenyl]-acetic acid (56) (8.6 mg, 13% for 2 steps) as a white solid; EI(+)-HRMS m/z calcd for C16H16Cl2N2O3 (M+H)+ 355.0611, found 355.0611. MW=355.2235, Exact Mass=354.0538

来源

DOI: 10.6084/m9.figshare.5104873.v1专利: USRE046024E1uspto-grants-2016_06