Ethyl bromoacetate → 2-(4-chlorophenyl)-6-carboxymethoxy-4-methyl-2H-1,2,4-benzothiadiazine-3(4H)-one 1,1-dioxide

HRID 477885Notes

Reaction equation

HRID 477885 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:13](=[O:14])[N:12]([CH3:15])[C:11]3[CH:16]=[C:17]([OH:20])[CH:18]=[CH:19][C:10]=3[S:9]2(=[O:22])=[O:21])=[CH:4][CH:3]=1.Br[CH2:24][C:25]([O:27]CC)=[O:26].C(=O)([O-])[O-].[K+].[K+]>CN(C)C=O>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:13](=[O:14])[N:12]([CH3:15])[C:11]3[CH:16]=[C:17]([O:20][CH2:24][C:25]([OH:27])=[O:26])[CH:18]=[CH:19][C:10]=3[S:9]2(=[O:21])=[O:22])=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 7748Ethyl bromoacetateHCID 11430Potassium CarbonateHCID 198724772-(4-chlorophenyl)-6-hydroxy-4-methyl-2H-1,2,4-benzothiadiazine-3(4H)-one 1,1-dioxide

Product 1

HCID 198724632-(4-chlorophenyl)-6-carboxymethoxy-4-methyl-2H-1,2,4-benzothiadiazine-3(4H)-one 1,1-dioxide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of 2-(4-chlorophenyl)-6-hydroxy-4-methyl-2H-1,2,4-benzothiadiazine-3(4H)-one 1,1-dioxide (500 mg), ethyl bromoacetate (0.2 ml), and potassium carbonate (245 mg) in N,N-dimethyl formamide (1 ml) was stirred at 80° C. for 3 hours. The mixture was cooled and poured into ice-water. The separated solid was filtered and dissolved in a mixture of ethanol (15 ml) and tetrahydrofuran (15 ml). To the solution containing 2-(4-chlorophenyl)-6-ethoxycarbonylmethoxy-4-methyl-2H-1,2,4-benzothiadiazine-3(4H)-one 1,1-dioxide was added aqueous 1N-sodium hydroxide solution (2.2 ml) in one portion at ambient temperature. The solution was stirred for one hour at ambient temperature and concentrated in vacuo. The residue was extracted with methylene chloride. The organic layer washed with brine, dried, and evaporated to give the crude product, which was crystallized from methanol to yield 2-(4-chlorophenyl)-6-carboxymethoxy-4-methyl-2H-1,2,4-benzothiadiazine-3(4H)-one 1,1-dioxide (213 mg).

Workup

  1. temperatureThe mixture was cooled
  2. filtrationThe separated solid was filtered
  3. dissolutiondissolved in a mixture of ethanol (15 ml) and tetrahydrofuran (15 ml)
  4. additionTo the solution containing 2-(4-chlorophenyl)-6-ethoxycarbonylmethoxy-4-methyl-2H-1,2,4-benzothiadiazine-3(4H)-one 1,1-dioxide
  5. additionwas added aqueous 1N-sodium hydroxide solution (2.2 ml) in one portion at ambient temperature
  6. stirringThe solution was stirred for one hour at ambient temperature
  7. concentrationconcentrated in vacuo
  8. extractionThe residue was extracted with methylene chloride
  9. washThe organic layer washed with brine
  10. customdried
  11. customevaporated
  12. customto give the crude product, which
  13. customwas crystallized from methanol

Sources & evidence

ORD record
ord-f4d728376847407cb03647d100ce026c
Source dataset
uspto-grants-1989_12
Patent number
US04889851

Reaction notes

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