Acetic Acid → N-(N-formyl-N-methyl-aminomethyl)-3,4-dichloroisothiazole-5-carboxamide

HRID 642918Notes

Reaction equation

HRID 642918 reaction equation
[CH:1]([N:3]([CH3:6])[CH2:4][OH:5])=O.[Cl:7][C:8]1[C:12]([Cl:13])=[C:11]([C:14]([NH2:16])=[O:15])[S:10][N:9]=1.C(O)(=O)C.S(=O)(=O)(O)O>O>[CH:4]([N:3]([CH2:1][NH:16][C:14]([C:11]1[S:10][N:9]=[C:8]([Cl:7])[C:12]=1[Cl:13])=[O:15])[CH3:6])=[O:5]

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 1118Sulfuric AcidHCID 107853N-(Hydroxymethyl)-N-methylformamideHCID 113330673,4-Dichloro-5-isothiazolecarboxylic acid amide

Product 1

HCID 9860156N-(N-formyl-N-methyl-aminomethyl)-3,4-dichloroisothiazole-5-carboxamideYield 47.1%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

At room temperature, 15 g (0.164 mol) of N-formyl-N-hydroxymethyl-methylamine are added with stirring to a mixture of 32.3 g (0.164 mol) of 3,4-dichloro-isothiazole-5-carboxamide and 245 ml of glacial acetic acid. At room temperature, 37 g (0.362 mol) of concentrated sulphuric acid are then added dropwise with stirring, the reaction mixture being cooled with ice. The reaction mixture is subsequently stirred at room temperature for 29 hours and then, with ice-cooling, admixed with 400 ml of water. The resulting mixture is extracted four times with 200 ml of methylene chloride and the combined organic phases are dried over sodium sulphate and then concentrated under reduced pressure. The oily residue that remains is chromatographed over silica gel using ethyl acetate. Concentration of the eluate gives 20.7 g (42.6% of theory) of N—(N-formyl-N-methyl-aminomethyl)-3,4-dichloro-isothiazole-5-carboxamide in the form of a crystalline solid of melting point 87 to 88° C.

Workup

  1. temperaturethe reaction mixture being cooled with ice
  2. stirringThe reaction mixture is subsequently stirred at room temperature for 29 hours
  3. extractionThe resulting mixture is extracted four times with 200 ml of methylene chloride
  4. dry with materialthe combined organic phases are dried over sodium sulphate
  5. concentrationconcentrated under reduced pressure
  6. customThe oily residue that remains is chromatographed over silica gel

Sources & evidence

ORD record
ord-9ebc86a3943146d48a4240e0bf05271c
Source dataset
uspto-grants-2010_04
Patent number
US07696355B2

Reaction notes

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