Hydrochloric Acid → 4-{5-(4-cyanophenyl)-2-methylbenzyl}-5-methoxy-2-methyl-2,4-dihydro-3H-1,2,4-triazol-3-one

HRID 2296992Notes

Reaction equation

HRID 2296992 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]([CH3:18])=[C:6]([CH:17]=1)[CH2:7][N:8]1[C:12]([O:13][CH3:14])=[N:11][N:10]([CH3:15])[C:9]1=[O:16].Cl[C:20]1[CH:27]=[CH:26][C:23]([C:24]#[N:25])=[CH:22][CH:21]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.Cl>N1C=CC=CC=1.[Ni](Cl)Cl.[Zn].C(OCC)(=O)C>[C:24]([C:23]1[CH:26]=[CH:27][C:20]([C:2]2[CH:3]=[CH:4][C:5]([CH3:18])=[C:6]([CH:17]=2)[CH2:7][N:8]2[C:12]([O:13][CH3:14])=[N:11][N:10]([CH3:15])[C:9]2=[O:16])=[CH:21][CH:22]=1)#[N:25]

Participants

9

Reactant 4

HCID 313Hydrochloric AcidHCID 11776TriphenylphosphineHCID 121634-ChlorobenzonitrileHCID 120565184-(5-bromo-2-methylbenzyl)-5-methoxy-2-methyl-2,4-dihydro-3H-1,2,4-triazol-3-one

Product 1

HCID 183888734-{5-(4-cyanophenyl)-2-methylbenzyl}-5-methoxy-2-methyl-2,4-dihydro-3H-1,2,4-triazol-3-oneYield 33.7%

Reagents, catalysts & solvents 4

HCID 23994ZincCatalystHCID 24385Nickel DichlorideCatalystHCID 1049PyridineSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of 1.80 g (5.77 mmol) of 4-(5-bromo-2-methylbenzyl)-5-methoxy-2-methyl-2,4-dihydro-3H-1,2,4-triazol-3-one (the compound 299 of the present invention), 0.89 g (5.77 mmol) of 4-chlorobenzonitrile, 75 mg (0.577 mmol) of anhydrous nickel (II) chloride, and 0.31 g (1.15 mmol) of triphenylphosphine in 6 ml of pyridine was heated to 80° C. under an atmosphere of nitrogen. Then, 0.79 g (12.1 mmol) of zinc powder was added thereto, and the mixture was stirred at 80° C. under an atmosphere of nitrogen for 5 hours. After cooling to room temperature, the mixture was poured into a mixture of diluted hydrochloric acid (prepared by mixing 72 ml of water and 8 ml of concentrated hydrochloric acid) and ice, and ethyl acetate was added thereto. The resultant mixture was filtered with cotton and separated, and the organic layer was washed successively with an aqueous solution of sodium bicarbonate and water, then dried and concentrated. The residue (2.17 g) was subjected to silica gel column chromatography (eluted with hexane:ethyl acetate=2:1and then 1:1 for eluting impurities and then 1:2 for eluting the desired compound) to obtain 0.65 g of 4-{5-(4-cyanophenyl)-2-methylbenzyl}-5-methoxy-2-methyl-2,4-dihydro-3H-1,2,4-triazol-3-one (the compound 489 of the present invention) as crystals.

Workup

  1. temperatureAfter cooling to room temperature
  2. additionwas added
  3. filtrationThe resultant mixture was filtered with cotton
  4. customseparated
  5. washthe organic layer was washed successively with an aqueous solution of sodium bicarbonate and water
  6. customdried
  7. concentrationconcentrated
  8. washeluted with hexane
  9. washethyl acetate=2:1and then 1:1 for eluting impurities
  10. wash1:2 for eluting the desired compound)

Sources & evidence

ORD record
ord-d4989e9d20f24f8ab7157edf926dbf66
Source dataset
uspto-grants-2002_12
Patent number
US06489487B1

Reaction notes

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