Hydrochloric Acid → HCID 117736906, compound

HRID 1504549Notes

Reaction equation

HRID 1504549 reaction equation
C(S[C:9]1[CH:10]=[CH:11][C:12]([I:22])=[C:13](/[CH:15]=[CH:16]/[C:17]([O:19][CH2:20][CH3:21])=[O:18])[CH:14]=1)C1C=CC=CC=1.ClN1C(C)(C)C(=O)N(Cl)C1=O.[S:34](Cl)(Cl)(=[O:36])=[O:35].N1CC(=O)NC1=O.S(=O)(O)[O-].[Na+].[NH2:51][C:52]1[CH:56]=[CH:55][O:54][N:53]=1.N1C=CC=CC=1.Cl>C(#N)C.CCOC(C)=O.O.C(O)(=O)C>[I:22][C:12]1[CH:11]=[CH:10][C:9]([S:34](=[O:36])(=[O:35])[NH:51][C:52]2[CH:56]=[CH:55][O:54][N:53]=2)=[CH:14][C:13]=1/[CH:15]=[CH:16]/[C:17]([O:19][CH2:20][CH3:21])=[O:18]

Participants

13

Reactant 8

HCID 313Hydrochloric AcidHCID 1049PyridineHCID 83601,3-Dichloro-5,5-dimethylhydantoinHCID 10006HydantoinHCID 24648Sulfuryl chlorideHCID 18102163-IsoxazolamineHCID 23665763Sodium BisulfiteHCID 131734331HCID 131734331, compound

Product 1

HCID 117736906HCID 117736906, compoundYield 36.2%

Reagents, catalysts & solvents 4

HCID 176Acetic AcidSolventHCID 962WaterSolvent2×HCID 6342AcetonitrileSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

(E)-Ethyl 3-(5-(benzylthio)-2-iodophenyl)acrylate (0.225 g, 0.265 mmol) was added to a vial and dissolved in acetonitrile (2.494 ml). Acetic acid (0.095 ml) and water (0.062 ml) were added and the vial was cooled to 0° C. 1,3-dichloro-5,5-dimethylhydantoin (0.057 g, 0.292 mmol) was then added as a solid in one portion while 0° C. was maintained. After 20 min. LC/MS showed mass corresponding to sulfoxide (mono-oxidation) along with sulfonyl chloride. After 1 hr. an additional 0.2 equiv (10 mg) of hydantoin was added. After an additional 20 min. the oxidation was complete. Solid sodium bisulfite was added and the reaction was diluted with EtOAc and water and stirred for 5 min. The organic layer was separated, the aq. re-extracted 2× with EtOAc, and the organic layers combined. After washing with brine, drying with Na2SO4, and concentrating, the crude residue was brought up in 1.5 mL of DCM and treated with 3-aminoisoxazole (0.039 ml, 0.530 mmol) and pyridine (0.107 ml, 1.326 mmol) After 45 min, the reaction was poured into 1N HCl and extracted 2× with EtOAc. The combined organics were washed with brine, dried over Na2SO4, and concentrated to give an orange solid that was purified by MPLC (25 g puriflash, 25-85% EtOAC:Heptanes) to give (E)-ethyl 3-(2-iodo-5-(N-(isoxazol-3-yl)sulfamoyl)phenyl)acrylate (0.043 g, 0.096 mmol, 36.2% yield) as a white solid. m/z (ESI) 447.0 (M−H)−.

Workup

  1. temperaturewas maintained
  2. waitAfter 1 hr
  3. waitAfter an additional 20 min. the oxidation was complete
  4. customThe organic layer was separated
  5. extractionthe aq. re-extracted 2× with EtOAc
  6. washAfter washing with brine
  7. dry with materialdrying with Na2SO4
  8. concentrationconcentrating
  9. extractionextracted 2× with EtOAc
  10. washThe combined organics were washed with brine
  11. dry with materialdried over Na2SO4
  12. concentrationconcentrated
  13. customto give an orange solid
  14. customthat was purified by MPLC (25 g puriflash, 25-85% EtOAC:Heptanes)

Sources & evidence

ORD record
ord-cfffedba149a44c5bfa87e2c0f3c5d1f
Source dataset
uspto-grants-2015_12
Patent number
US09212182B2

Reaction notes

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