Phosgene → 4-(4-methoxyphenyl)-alpha-methyl-4H-1,2,4-triazol-3-methanol

HRID 1197875Notes

Reaction equation

HRID 1197875 reaction equation
C([N:3]([CH2:6][CH3:7])[CH2:4]C)C.CN(C)[C:10]1([O:25][CH3:26])[CH:24]=CC(C(NC2C=CC=CC=2)=O)=[CH:12][CH2:11]1.C(Cl)(Cl)=O.[C:32]([NH:37][NH2:38])(=O)[CH:33]([CH3:35])[OH:34]>C(Cl)Cl.C1(C)C=CC=CC=1.CN(C)C=O>[CH3:26][O:25][C:10]1[CH:24]=[CH:7][C:6]([N:3]2[CH:4]=[N:38][N:37]=[C:32]2[CH:33]([CH3:35])[OH:34])=[CH:12][CH:11]=1

Participants

8

Reactant 4

HCID 6371PhosgeneHCID 8471TriethylamineHCID 3120432-HydroxypropanehydrazideHCID 678489844-Dimethylamino-4-methoxybenzanilide

Product 1

HCID 704603594-(4-methoxyphenyl)-alpha-methyl-4H-1,2,4-triazol-3-methanol

Reagents, catalysts & solvents 3

HCID 1140TolueneSolvent2×HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
-40 °C

Procedure

2.36 g of triethylamine were added to a suspension of 5 g of 4-dimethylamino-4-methoxy benzanilide (prepared as in Example 12) in 50 ml of methylene chloride and the mixture was cooled to -40° C. Then over 20 minutes and under an inert atmosphere, a solution of 5.75 ml of phosgene in toluene is added, and the mixture was re-heated to 20° C. over 90 minutes. The solution obtained was introduced into 200 ml of refluxing toluene and simultaneously a solution of 2.9 g of lactic acid hydrazide (DL form) in 6 ml of dimethylformamide was added. A part of the solvents was eliminated by distilling and then, after heating for 30 minutes to 107°-110° C., the reaction mixture was cooled and washed first with water, then with an N aqueous solution of sodium hydroxide and again with water. After extracting with methylene chloride and concentrating to dryness, 7.1 g of crude product were obtained which was crystallized from a mixture of ethyl acetylacetate and isopropyl ether (3-6) and then from pure ethyl acetate to obtain 5-[4-dimethylamino)phenyl]-4-(4-methoxyphenyl)-α-methyl-4H-1,2,4-triazol-3-methanol melting at 170° C.

Workup

  1. temperaturethe mixture was re-heated to 20° C. over 90 minutes
  2. customThe solution obtained
  3. distillationby distilling
  4. temperatureafter heating for 30 minutes to 107°-110° C.
  5. temperaturethe reaction mixture was cooled
  6. washwashed first with water
  7. extractionAfter extracting with methylene chloride
  8. concentrationconcentrating to dryness
  9. custom7.1 g of crude product were obtained which
  10. customwas crystallized from a mixture of ethyl acetylacetate and isopropyl ether (3-6)

Sources & evidence

ORD record
ord-3345391c2ef4425aa8d91546587e5733
Source dataset
uspto-grants-1994_01
Patent number
US05278180

Reaction notes

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