Triethylamine → 5-difluoromethyl-2-methyl-4-{2-methyl-5-(3-methyl-methoxy-1-butynyl)-benzyl)-2,4-dihydro-3H-1,2,4-triazol-3-one

HRID 1883627Notes

Reaction equation

HRID 1883627 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].C[C:21]([O:25][CH3:26])(C)[C:22]#[CH:23].[C:27]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C[CH:28]=1.C(N(CC)CC)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.COC(C)(C)C.C(#N)C>[F:14][CH:13]([F:15])[C:12]1[N:8]([CH2:7][C:6]2[CH:18]=[C:2]([C:27]#[C:28][CH:22]([CH3:23])[CH2:21][O:25][CH3:26])[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 8471TriethylamineHCID 11776TriphenylphosphineHCID 49132563-Methoxy-3-methylbut-1-yneHCID 129940064-(5-bromo-2-methylbenzyl)-5-difluoromethyl-2-methyl-2,4-dihydro-3H-1,2,4-triazol-3-one2×

Product 1

HCID 1317244995-difluoromethyl-2-methyl-4-{2-methyl-5-(3-methyl-methoxy-1-butynyl)-benzyl)-2,4-dihydro-3H-1,2,4-triazol-3-oneYield 686.9%

Reagents, catalysts & solvents 4

HCID 83717Copper iodideCatalystHCID 178418476HCID 178418476, compoundCatalystHCID 6342AcetonitrileSolventHCID 15413tert-Butyl methyl etherSolvent

Procedure

498 mg (1.5 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 (1.2 mmol) of 3-methyl-3-methoxy-1-butine, 21.1 mg (0.030 mmol) of PdCl2(PPh3)2, 19.0 mg (0.050 mmol) of copper iodide, 39.3 mg (0.15 mmol) of triphenylphosphine, 607 mg of triethylamine and 6.0 ml of acetonitrile were mixed, and the mixture was heated under reflux for 4.5 hours in nitrogen atmosphere. After cooling to room temperature, t-butyl methyl ether was added to the reaction solution, and the mixture was filtrated through celite, then, concentrated under reduced pressure. The residue was subjected to silica gel column chromatography (eluant: hexane/ethyl acetate=2/1 (v/v)) to obtain 360 mg of 5-difluoromethyl-2-methyl-4-{2-methyl-5-(3-methyl-methoxy-1-butynyl)-benzyl)-2,4-dihydro-3H-1,2,4-triazol-3-one (Compound 326).

Workup

  1. temperaturethe mixture was heated
  2. temperatureunder reflux for 4.5 hours in nitrogen atmosphere
  3. filtrationthe mixture was filtrated through celite
  4. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-f3c8c7914d304070ac449f90d25c0cec
Source dataset
uspto-grants-2004_07
Patent number
US06762197B2

Reaction notes

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