Ethyl chloroformate → 1-(4-Chlorophenyl)-1,4-dihydro-3-methylsulfonamidocarbonyl-4-oxo-6-methylpyridazine

HRID 638479Notes

Reaction equation

HRID 638479 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:13]([CH3:14])=[CH:12][C:11](=[O:15])[C:10]([C:16]([OH:18])=O)=[N:9]2)=[CH:4][CH:3]=1.ClC(OCC)=O.[Li].[CH3:26][S:27]([NH2:30])(=[O:29])=[O:28]>C1COCC1.CCOCC.C(N(CC)CC)C>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:13]([CH3:14])=[CH:12][C:11](=[O:15])[C:10]([C:16]([NH:30][S:27]([CH3:26])(=[O:29])=[O:28])=[O:18])=[N:9]2)=[CH:4][CH:3]=1

Participants

8

Reactant 4

HCID 10928Ethyl chloroformateHCID 72879Methanesulfonamide2×HCID 197225FenridazonHCID 3028194Lithium

Product 1

HCID 202523691-(4-Chlorophenyl)-1,4-dihydro-3-methylsulfonamidocarbonyl-4-oxo-6-methylpyridazineYield 71.8%

Reagents, catalysts & solvents 3

HCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent2×HCID 8471TriethylamineSolvent

Conditions

Temperature
-78 °C

Procedure

To a mixture of 1.3 g of 1-(4-chlorophenyl)-1,4-dihydro-4-oxo-6-methylpyridazine-3-carboxylic acid and 0.73 ml of triethylamine in 50 ml of THF was added at -40° C., 0.53 ml of ethyl chloroformate, and the resulting mixture was allowed to reach room temperature over 2 hours with continued stirring. The mixture was then cooled to -78° C., and the monolithium salt of methanesulfonamide (prepared from 18 mmole of lithiodiisopropylamide and 15 mmole (1.42 g) of methanesulfonamide) in 25 ml of THF was added dropwise at -65° C. The resulting slurry was allowed to reach room temperature with continual stirring. After an additional hour of stirring the reaction mixture was diluted with 200 ml of ether and washed with 1N hydrochloric acid. The ether layer was then extracted with 5% sodium bicarbonate and the aqueous phase was acidified to pH2. The resulting precipitate was collected by filtration and recrystallized from methanol to yield 1.206 g of product, m.p. 225°-227°.

Workup

  1. additionwas added at -40° C.
  2. customto reach room temperature with continual stirring
  3. washwashed with 1N hydrochloric acid
  4. extractionThe ether layer was then extracted with 5% sodium bicarbonate
  5. filtrationThe resulting precipitate was collected by filtration
  6. customrecrystallized from methanol

Sources & evidence

ORD record
ord-8af0b5a4d8ac4bef9e0f46f609005a1d
Source dataset
uspto-grants-1985_12
Patent number
US04561881

Reaction notes

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