Hydrochloric Acid → (1,1-Dioxo-1,4-dihydro-1lambda6-benzo[1,2,4]thiadiazin-3-yl)-acetic acid

HRID 731366Notes

Reaction equation

HRID 731366 reaction equation
Cl[C:2](=O)[CH2:3][C:4]([O:6]C)=[O:5].[NH2:9][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=1[S:16]([NH2:19])(=[O:18])=[O:17].[OH-].[Na+].Cl>C(OCC)C.CN(C)C(=O)C>[O:17]=[S:16]1(=[O:18])[C:11]2[CH:12]=[CH:13][CH:14]=[CH:15][C:10]=2[NH:9][C:2]([CH2:3][C:4]([OH:6])=[O:5])=[N:19]1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 728942-AminobenzenesulfonamideHCID 123460Methyl malonyl chloride

Product 1

HCID 11708529(1,1-Dioxo-1,4-dihydro-1lambda6-benzo[1,2,4]thiadiazin-3-yl)-acetic acidYield 93.3%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 31374DimethylacetamideSolvent

Conditions

Temperature
0 °C

Procedure

Methyl 3-chloro-3-oxopropionate (3.36 mL, 31.3 mmol) was added to a solution of 2-aminobenzenesulfonamide (4.91 g, 28.5 mmol) in a 1:1 mixture of N,N-dimethylacetamide and diethylether (100 mL) at 0° C. The cloudy reaction mixture was stirred at 0° C. for 3 h, and then was partitioned between half-saturated aqueous sodium bicarbonate (150 mL) and ethyl acetate (2×150 mL). The organic layers were dried over sodium sulfate, filtered and were concentrated in vacuo. The residue was then dissolved in water (75 mL) containing sodium hydroxide (3.42 g, 85.5 mmol) at 25° C. The mixture was heated at 100° C. for 1 h, and then was cooled to 0° C. Concentrated (12.0 M) aqueous hydrochloric acid solution (10.0 mL, 120 mmol) was added dropwise via addition funnel over 10 min, resulting in the formation of a white precipitate. The reaction mixture was stirred at 0° C. for an additional 15 min, and then was filtered through a medium frit. The collected material was washed with water (30 mL) and was air-dried overnight to afford the desired product, (1,1-dioxo-1,4-dihydro-1λ6-benzo[1,2,4]thiadiazin-3-yl)-acetic acid (6.37 g, 26.6 mmol, 93%), as a white solid. 1H NMR (400 MHz, DMSO-d6) δ: 3.58 (2H, s), 7.30 (1H, d, J=7.4 Hz), 7.44 (1H, t, J=8.2 Hz), 7.64-7.68 (1H, m), 7.79 (1H, dd, J1=1.5 Hz, J2=7.8 Hz), 12.19 (1H, s).

Workup

  1. customThe cloudy reaction mixture
  2. customwas partitioned between half-saturated aqueous sodium bicarbonate (150 mL) and ethyl acetate (2×150 mL)
  3. dry with materialThe organic layers were dried over sodium sulfate
  4. filtrationfiltered
  5. concentrationwere concentrated in vacuo
  6. dissolutionThe residue was then dissolved in water (75 mL)
  7. temperatureThe mixture was heated at 100° C. for 1 h
  8. temperaturewas cooled to 0° C
  9. additionwas added dropwise via addition funnel over 10 min
  10. customresulting in the formation of a white precipitate
  11. stirringThe reaction mixture was stirred at 0° C. for an additional 15 min
  12. filtrationwas filtered through a medium frit
  13. washThe collected material was washed with water (30 mL)
  14. customwas air-dried overnight

Sources & evidence

ORD record
ord-fd1460748cb644f8808b0c6115d41d60
Source dataset
uspto-grants-2009_09
Patent number
US07582626B2

Reaction notes

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