Acetonitrile → 5-difluoromethyl-4-{5-(3-ethyl-3-methoxy-1-pentynyl)-2-methylbenzyl)-2-methyl-2,4-dihydro-3H-1,2,4-triazol-3-one

HRID 1883625Notes

Reaction equation

HRID 1883625 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]([CH3:19])=[C:6]([CH:18]=1)[CH2:7][N:8]1[C:12]([CH:13]([F:15])[F:14])=[N:11][N:10]([CH3:16])[C:9]1=[O:17].[CH2:20]([C:22]([O:27][CH3:28])([CH2:25][CH3:26])[C:23]#[CH:24])[CH3:21].C(N(CC)CC)C.C(#N)C>Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.[Cu](I)I.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.COC(C)(C)C>[F:14][CH:13]([F:15])[C:12]1[N:8]([CH2:7][C:6]2[CH:18]=[C:2]([C:21]#[C:20][C:22]([CH2:25][CH3:26])([O:27][CH3:28])[CH2:23][CH3:24])[CH:3]=[CH:4][C:5]=2[CH3:19])[C:9](=[O:17])[N:10]([CH3:16])[N:11]=1

Participants

9

Reactant 4

HCID 6342AcetonitrileHCID 8471TriethylamineHCID 5660771-Pentyne, 3-ethyl-3-methoxy-HCID 129940064-(5-bromo-2-methylbenzyl)-5-difluoromethyl-2-methyl-2,4-dihydro-3H-1,2,4-triazol-3-one2×

Product 1

HCID 235082285-difluoromethyl-4-{5-(3-ethyl-3-methoxy-1-pentynyl)-2-methylbenzyl)-2-methyl-2,4-dihydro-3H-1,2,4-triazol-3-oneYield 84.5%

Reagents, catalysts & solvents 4

HCID 11776TriphenylphosphineCatalystHCID 83717Copper iodideCatalystHCID 178418476HCID 178418476, compoundCatalystHCID 15413tert-Butyl methyl etherSolvent

Procedure

332 mg (1.00 mmol) of 4-(5-bromo-2-methylbenzyl)-5-difluoromethyl-2-methyl-2,4-dihydro-3H-1,2,4-triazol-3-one (Compound 40), 378 mg (3.00 mmol) of 3-ethyl-3-methoxy-1-pentine, 14 mg (0.020 mmol) of PdCl2(PPh3)2, 9.5 mg (0.050 mmol) of copper iodide (I), 15.7 mg (0.060 mmol) of triphenylphosphine and 0.5 ml of triethylamine were added to 4.0 ml of acetonitrile, and the mixture was heated under reflux for 5 hours in nitrogen atmosphere. After cooling to room temperature, t-butyl methyl ether was added to the reaction solution, and the mixture was washed with water and dried over anhydrous magnesium sulfate, then, concentrated under reduced pressure. The residue was subjected to silica gel column chromatography (eluant: hexane/ethyl acetate=2/1 (v/v)), to obtain 319 mg of 5-difluoromethyl-4-{5-(3-ethyl-3-methoxy-1-pentynyl)-2-methylbenzyl}-2-methyl-2,4-dihydro-3H-1,2,4-triazol-3-one (Compound 277).

Workup

  1. temperaturethe mixture was heated
  2. temperatureunder reflux for 5 hours in nitrogen atmosphere
  3. washthe mixture was washed with water
  4. dry with materialdried over anhydrous magnesium sulfate
  5. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-f5ccff407d1c4cce9bfac854c4df7d41
Source dataset
uspto-grants-2004_07
Patent number
US06762197B2

Reaction notes

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