Ethyl 3-chloro-3-oxopropionate → (7-Iodo-1,1-dioxo-1,4-dihydro-1lambda6-benzo[1,2,4]thiadiazin-3-yl)-acetic acid

HRID 2374366Notes

Reaction equation

HRID 2374366 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([I:8])=[CH:4][C:3]=1[S:9]([NH2:12])(=[O:11])=[O:10].Cl[C:14](=O)[CH2:15][C:16]([O:18]CC)=[O:17]>CN(C)C(=O)C.C(OCC)C.O>[I:8][C:5]1[CH:6]=[CH:7][C:2]2[NH:1][C:14]([CH2:15][C:16]([OH:18])=[O:17])=[N:12][S:9](=[O:11])(=[O:10])[C:3]=2[CH:4]=1

Participants

6

Reactant 2

HCID 118931Ethyl 3-chloro-3-oxopropionateHCID 223240882-Amino-5-iodobenzenesulfonamide

Product 1

HCID 59853574(7-Iodo-1,1-dioxo-1,4-dihydro-1lambda6-benzo[1,2,4]thiadiazin-3-yl)-acetic acidYield 81.4%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 3283Diethyl EtherSolvent2×HCID 31374DimethylacetamideSolvent

Conditions

Temperature
25 °C

Procedure

2-Amino-5-iodo-benzenesulfonamide (Example 4a, 2.0 g, 6.71 mmol) was dissolved in N,N-dimethylacetamide (5 mL) and diethyl ether (7 mL). Ethyl 3-chloro-3-oxo-propionate (0.916 g, 6.71 mmol) was added and the reaction mixture was stirred at 25° C. for 2 h. The reaction mixture was diluted with diethyl ether (10 mL) and water (20 mL). Upon mixing vigorously, a precipitate formed. The solid was collected by vacuum filtration, rinsed with 1.0 M aqueous hydrochloric acid solution (2×10 mL) and dried in vacuo for 2 h. The solid was dissolved in 8% aqueous sodium hydroxide solution (50 mL) and stirred at 100° C. for 15 min. Upon cooling to 25° C., the solution was neutralized with 6.0 M aqueous hydrochloric acid solution. Additional 1.0 M aqueous hydrochloric acid solution (20 mL) was added and the desired product precipitated. The solid was collected by vacuum filtration, rinsed with 1.0 M aqueous hydrochloric acid solution (2×10 mL) and dried in vacuo for 16 h to afford the desired product, (7-iodo-1,1-dioxo-1,4-dihydro-1λ6-benzo[1,2,4]thiadiazin-3-yl)-acetic acid (2.0 g, 5.46 mmol, 81% yield) as a pale pink powder. 1HNMR (400 MHz, DMSO-d6) δ: 3.58 (3H, s), 7.13 (1H, d, J=8.5 Hz), 7.98 (1H, dd, J1=8.6 Hz, J2=1.7 Hz), 8.03 (1H, d, J=2.5 Hz), 12.33 (1H, bs), 13.05 (1H, bs). LC-MS (ESI) calcd for C9H7IN2O4S 365.92. found 366.95 [M+H+].

Workup

  1. additionUpon mixing vigorously
  2. customa precipitate formed
  3. filtrationThe solid was collected by vacuum filtration
  4. washrinsed with 1.0 M aqueous hydrochloric acid solution (2×10 mL)
  5. customdried in vacuo for 2 h
  6. dissolutionThe solid was dissolved in 8% aqueous sodium hydroxide solution (50 mL)
  7. stirringstirred at 100° C. for 15 min
  8. temperatureUpon cooling to 25° C.
  9. additionAdditional 1.0 M aqueous hydrochloric acid solution (20 mL) was added
  10. customthe desired product precipitated
  11. filtrationThe solid was collected by vacuum filtration
  12. washrinsed with 1.0 M aqueous hydrochloric acid solution (2×10 mL)
  13. customdried in vacuo for 16 h

Sources & evidence

ORD record
ord-7aa159ea004849e5856165b67937e6f0
Source dataset
uspto-grants-2008_12
Patent number
US07462611B2

Reaction notes

Loading…