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

HRID 2296990Notes

Reaction equation

HRID 2296990 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].[C:19]([O-])(=[O:21])[CH3:20].[Tl+].C(OCCCC)=C.C1(P(C2C=CC=CC=2)CCCP(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(N(CC)CC)C.Cl>CN(C)C=O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[C:19]([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])(=[O:21])[CH3:20]

Participants

9

Reactant 6

HCID 313Hydrochloric AcidHCID 8108Butyl vinyl etherHCID 8471TriethylamineHCID 11247thallium(I) acetateHCID 812191,3-Bis(diphenylphosphino)propaneHCID 120565184-(5-bromo-2-methylbenzyl)-5-methoxy-2-methyl-2,4-dihydro-3H-1,2,4-triazol-3-one

Product 1

HCID 183888414-(5-acetyl-2-methylbenzyl)-5-methoxy-2-methyl-2,4-dihydro-3H-1,2,4-triazol-3-oneYield 64.2%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
90 °C

Procedure

To a solution of 4.56 g (14.6 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) in 30 ml of N,N-dimethylformamide were added 4.20 g (16 mmol) of thallium (I) acetate, 9.34 ml (72.6 mmol) of butyl vinyl ether, 604 mg (3.64 mmol) of 1,3-bis(diphenylphosphino)propane, 160 mg (0.72 mmol) of palladium (II) acetate and 2.44 ml (17.5 mmol) of triethylamine and the mixture was stirred at 90° C. under an atmosphere of nitrogen for 8 hours. After the reaction mixture was cooled to room temperature, diluted hydrochloric acid (prepared by mixing 21 ml of concentrated hydrochloric acid and 130 ml of water) was added thereto, and the mixture was stirred for 30 minutes. The reaction mixture was filtered with cotton and washed with chloroform, and the filtrate was separated. After the water layer was extracted with chloroform once again, the organic layers were combined, washed with water (twice), dried and concentrated. Then, to the semisolid residue was added a mixture of equal amounts of tert-butyl methyl ether and hexane and the mixture was stirred at room temperature for a while. The solid was collected by filtration to obtain 2.58 g of 4-(5-acetyl-2-methylbenzyl)-5-methoxy-2-methyl-2,4-dihydro-3H-1,2,4-triazol-3-one (the compound 73 of the present invention) as pale yellow powder.

Workup

  1. temperatureAfter the reaction mixture was cooled to room temperature
  2. stirringthe mixture was stirred for 30 minutes
  3. filtrationThe reaction mixture was filtered with cotton
  4. washwashed with chloroform
  5. customthe filtrate was separated
  6. extractionAfter the water layer was extracted with chloroform once again
  7. washwashed with water (twice),
  8. customdried
  9. concentrationconcentrated
  10. additionThen, to the semisolid residue was added
  11. additiona mixture of equal amounts of tert-butyl methyl ether and hexane
  12. stirringthe mixture was stirred at room temperature for a while
  13. filtrationThe solid was collected by filtration

Sources & evidence

ORD record
ord-c821e0f413d14e948381ce73198f6a16
Source dataset
uspto-grants-2002_12
Patent number
US06489487B1

Reaction notes

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