Cesium carbonate → 4-(4-{[3-(ethyloxy)phenyl]oxy}phenyl)-5-methyl-2,4-dihydro-3H-1,2,4-triazol-3-one

HRID 1484523

Reaction equation

HRID 1484523 reaction equation
C(=O)([O-])[O-].[Cs+].[Cs+].[CH2:7]([O:9][C:10]1[CH:11]=[C:12]([OH:16])[CH:13]=[CH:14][CH:15]=1)[CH3:8].Br[C:18]1[CH:23]=[CH:22][C:21]([N:24]2[C:28]([CH3:29])=[N:27][NH:26][C:25]2=[O:30])=[CH:20][CH:19]=1.CC(C)(C(=O)CC(=O)C(C)(C)C)C>CN1C(=O)CCC1.[Cu](Cl)Cl>[CH2:7]([O:9][C:10]1[CH:11]=[C:12]([O:16][C:18]2[CH:19]=[CH:20][C:21]([N:24]3[C:28]([CH3:29])=[N:27][NH:26][C:25]3=[O:30])=[CH:22][CH:23]=2)[CH:13]=[CH:14][CH:15]=1)[CH3:8]

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 693063-EthoxyphenolHCID 707002,2,6,6-Tetramethyl-3,5-heptanedioneHCID 14877914-(4-bromophenyl)-3-methyl-4,5-dihydro-1H-1,2,4-triazol-5-one2×

Product 1

HCID 900239604-(4-{[3-(ethyloxy)phenyl]oxy}phenyl)-5-methyl-2,4-dihydro-3H-1,2,4-triazol-3-oneYield 6.6%

Reagents, catalysts & solvents 2

HCID 24014Cupric ChlorideCatalystHCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

To cesium carbonate (641 mg, 1.968 mmol, 2 equiv) was added 3-ethoxyphenol (272 mg, 1.968 mmol, 2 equiv) in 4 mL of NMP. The reaction mixture was degassed and filled with nitrogen 3 times (3 cycles vacuum/nitrogen). 4-(4-bromophenyl)-5-methyl-2,4-dihydro-3H-1,2,4-triazol-3-one (Intermediate 22, 250 mg, 0.984 mg, 1 equiv), 2,2,6,6-tetramethyl-3,5-heptanedione (18 mg, 0.098 mmol, 0.1 equiv) and copper chloride (58 mg, 0.590 mmol, 0.6 equiv) were added. The reaction mixture was degassed and filled with nitrogen 3 times (3 cycles vacuum/nitrogen) and then warmed to 120 C under nitrogen overnight. The reaction mixture was diluted with dichloromethane and filtered. Volatiles were removed in vacuo and the residue was purified by preparative HPLC to give the title compound (20.2 mg).

Workup

  1. customThe reaction mixture was degassed
  2. additionfilled with nitrogen 3 times (3 cycles vacuum/nitrogen)
  3. customThe reaction mixture was degassed
  4. additionfilled with nitrogen 3 times (3 cycles vacuum/nitrogen)
  5. temperaturewarmed to 120 C under nitrogen overnight
  6. additionThe reaction mixture was diluted with dichloromethane
  7. filtrationfiltered
  8. customVolatiles were removed in vacuo
  9. customthe residue was purified by preparative HPLC

Sources & evidence

ORD record
ord-2ac0da37bd484d5bae3e0c3966ac3876
Source dataset
uspto-grants-2016_08
Patent number
US09422252B2

Linked notes

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