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

HRID 1157230Notes

Reaction equation

HRID 1157230 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH2:20][CH2:21][O:22][C:23](=[O:25])[CH3:24])[CH:5]=[C:6]([Cl:19])[C:7]=1[O:8][C:9]1[CH:14]=[C:13]([CH:15]([CH3:17])[CH3:16])[C:12](=[O:18])[NH:11][N:10]=1.[C:26](=O)([O-])[O-].[K+].[K+].CI>>[Cl:1][C:2]1[CH:3]=[C:4]([CH2:20][CH2:21][O:22][C:23](=[O:25])[CH3:24])[CH:5]=[C:6]([Cl:19])[C:7]=1[O:8][C:9]1[CH:14]=[C:13]([CH:15]([CH3:17])[CH3:16])[C:12](=[O:18])[N:11]([CH3:26])[N:10]=1

Participants

4

Reactant 3

HCID 6328Methyl iodide2×HCID 11430Potassium Carbonate2×HCID 59834524Acetic acid 2-[3,5-dichloro-4-(5-isopropyl-6-oxo-1,6-dihydro-pyridazin-3-yloxy)-phenyl]-ethyl ester

Product 1

HCID 59834451Acetic acid 2-[3,5-dichloro-4-(5-isopropyl-1-methyl-6-oxo-1,6-dihydro-pyridazin-3-yloxy)-phenyl]-ethyl esterYield 72%

Conditions

Temperature
40 °C

Procedure

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

Workup

  1. temperatureThe mixture was heated at 40° C. for 2 h
  2. concentrationThe reaction mixture was concentrated
  3. customthe resulting residue was partitioned between ethyl acetate (50 mL) and water (25 mL)
  4. extractionThe water layer was re-extracted with ethyl acetate (25 mL)
  5. dry with materialdried with sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. dissolutionThe resulting residue was dissolved in 25% ethyl acetate in hexanes
  9. customwas purified by flash chromatography (Biotage 40S)
  10. washeluted with 25-50% ethyl acetate in hexanes
  11. customThe desired fractions were collected
  12. concentrationconcentrated under vacuum
  13. customThe resulting solid was dried under high vacuum

Sources & evidence

ORD record
ord-5e47e1c9999f4d22a2f5f36a688e13f0
Source dataset
uspto-grants-2010_10
Patent number
US07807674B2

Reaction notes

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