Dimethylformamide → HCID 67242996, compound

HRID 2421950Notes

Reaction equation

HRID 2421950 reaction equation
[CH2:1]([N:3]1[C:7](=[O:8])[C:6](O)=[C:5]([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)[S:4]1(=[O:17])=[O:16])[CH3:2].CN(C=O)C.C(Cl)(=O)C([Cl:26])=O>C(Cl)Cl>[Cl:26][C:6]1[C:7](=[O:8])[N:3]([CH2:1][CH3:2])[S:4](=[O:17])(=[O:16])[C:5]=1[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1

Participants

5

Reactant 3

HCID 6228Dimethylformamide2×HCID 65578Oxalyl chloride2×HCID 67242273HCID 67242273, compound2×

Product 1

HCID 67242996HCID 67242996, compoundYield 292.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

2-Ethyl-4-hydroxy-5-phenylisothiazol-3(2H)-one 1,1-dioxide (5 g, 19.76 mmol) was dissolved in dry DCM (250 mL) and cooled to 0° C. under N2. Dry DMF (15 mL) was added, followed by oxalyl chloride (3 mL, 34.4 mmol). The ice-bath was removed and the mixture was refluxed at 50° C. under N2 for 4 h. The reaction mixture was evaporated and the residue was diluted with EtOAc, washed with water (3×25 mL) and brine, dried over Na2SO4 and evaporated. Another (16 g, 63.24 mmol) of 2-ethyl-4-hydroxy-5-phenylisothiazol-3(2H)-one 1,1-dioxide was dissolved in dry DCM (500 mL) and cooled to 0° C. under N2. Dry DMF (20 mL) was added followed by oxalyl chloride (9 mL, 103.2 mmol). The ice-bath was removed and the mixture was refluxed at 50° C. under N2 for 4 h. The reaction mixture was evaporated and the residue was diluted with EtOAc, washed with water (3×50 mL) and brine, dried over Na2SO4 and evaporated where by red solid was obtained. The crude material from both batches were combined and purified by column chromatography on silica gel using 2.5-3% ethyl acetate in petroleum ether as eluant, and recrystallised from methanol to give the title compound (15.7 g, 70%) as a white solid; 1H NMR (400 MHz, CD3OD) δ 1.42 (t, 3H, J=7.3 Hz), 3.84 (q, 2H, J=7.3 Hz), 7.6-7.7 (m, 3H), 7.9-8.0 (m, 2H); Mass Spectrum: M+H+ 272.

Workup

  1. customThe ice-bath was removed
  2. temperaturethe mixture was refluxed at 50° C. under N2 for 4 h
  3. customThe reaction mixture was evaporated
  4. additionthe residue was diluted with EtOAc
  5. washwashed with water (3×25 mL) and brine
  6. dry with materialdried over Na2SO4
  7. customevaporated
  8. temperaturecooled to 0° C. under N2
  9. customThe ice-bath was removed
  10. temperaturethe mixture was refluxed at 50° C. under N2 for 4 h
  11. customThe reaction mixture was evaporated
  12. additionthe residue was diluted with EtOAc
  13. washwashed with water (3×50 mL) and brine
  14. dry with materialdried over Na2SO4
  15. customevaporated where by red solid
  16. customwas obtained
  17. custompurified by column chromatography on silica gel using 2.5-3% ethyl acetate in petroleum ether as eluant
  18. customrecrystallised from methanol

Sources & evidence

ORD record
ord-66548d78343d4709b51ba83d242aba17
Source dataset
uspto-grants-2011_06
Patent number
US07960380B2

Reaction notes

Loading…