2-Chloroethanol → HCID 86744860, compound

HRID 327714Notes

Reaction equation

HRID 327714 reaction equation
[N:1]1([C:6]2[CH:11]=[CH:10][C:9]([OH:12])=[CH:8][CH:7]=2)[CH:5]=[CH:4][N:3]=[CH:2]1.[Cl:13][CH2:14][CH2:15][OH:16].C(=O)([O-])[O-].[K+].[K+].C(N(CC)CC)C.[CH3:30][NH:31][S:32](Cl)(=[O:34])=[O:33]>C(C(C)=O)C.C(Cl)Cl.CO.C(Cl)Cl>[OH2:12].[ClH:13].[N:1]1([C:6]2[CH:11]=[CH:10][C:9]([O:12][CH2:14][CH2:15][O:16][S:32](=[O:34])(=[O:33])[NH:31][CH3:30])=[CH:8][CH:7]=2)[CH:5]=[CH:4][N:3]=[CH:2]1

Participants

9

Reactant 5

HCID 342-ChloroethanolHCID 8471TriethylamineHCID 11430Potassium CarbonateHCID 823151-(p-Hydroxyphenyl)imidazoleHCID 11789235N-Methylsulfamoyl chloride2×

Product 1

HCID 86744860HCID 86744860, compoundYield 28.9%

Reagents, catalysts & solvents 3

HCID 6344DichloromethaneSolventHCID 6569Methyl Ethyl KetoneSolventHCID 21226129Dichloromethane methanolSolvent

Conditions

Temperature
10 °C

Procedure

A solution of 4-imidazol-1-yl-phenol (20.0 g, 0.125 mole), 2-chloroethanol (40.25 g, 0.50 mole) and potassium carbonate (69.0 g, 0.50 mol) in 500 ml of methyl ethyl ketone was heated at reflux for 48 hr as its progress was being monitored by TLC (methanol:methylene chloride 10:90). The reaction was then filtered, and the filtrate evaporated to a solid which was redissolved in hot isopropanol. The crystals which formed upon cooling were filtered, rinsed with isopropyl ether, and dried (7.36 g, 28.9% yield, 1H NMR: 95% pure). This intermediate alcohol (6.0 g, 0.029 mole) was suspended in methylene chloride (60 ml) and triethylamine (3.51 g, 0.0348 mole) added to the stirring suspension. The reaction was chilled at 10° C. and methylsulfamoyl chloride (4.51 g, 0.0348 mole) added dropwise allowing reaction to slowly warm to room temperature. After 1 hr of stirring, TLC indicated reaction was not complete so it was treated with additional 0.03 mole of base and methylsulfamoyl chloride and stirred overnight. After the reaction had gone to completion, it was evaporated to a residue. The residue was dissolved in ethyl acetate/acetonitrile (1:1) (200 ml) and washed with sodium bicarbonate/sodium chloride (1:1) (2×200 ml). The organic layer was evaporated and redissolved in hot ethanol. Upon cooling, crystals precipitated and were filtered and dried. They were then dissolved in methanol and anhydrous HCl in isopropyl alcohol added. A carbon filtration was done and the methanol evaporated as more isopropanol was added. Off-white crystals precipitated and were filtered, dried, and analyzed (4.14 g, 42%, mp 85°-88° C.).

Workup

  1. temperatureat reflux for 48 hr as its progress
  2. filtrationThe reaction was then filtered
  3. customthe filtrate evaporated to a solid which
  4. dissolutionwas redissolved in hot isopropanol
  5. customThe crystals which formed
  6. temperatureupon cooling
  7. filtrationwere filtered
  8. washrinsed with isopropyl ether
  9. customdried (7.36 g, 28.9% yield, 1H NMR: 95% pure)
  10. customreaction
  11. temperatureto slowly warm to room temperature
  12. customreaction
  13. stirringstirred overnight
  14. customwas evaporated to a residue
  15. dissolutionThe residue was dissolved in ethyl acetate/acetonitrile (1:1) (200 ml)
  16. washwashed with sodium bicarbonate/sodium chloride (1:1) (2×200 ml)
  17. customThe organic layer was evaporated
  18. dissolutionredissolved in hot ethanol
  19. temperatureUpon cooling
  20. customcrystals precipitated
  21. filtrationwere filtered
  22. customdried
  23. dissolutionThey were then dissolved in methanol
  24. additionanhydrous HCl in isopropyl alcohol added
  25. filtrationA carbon filtration
  26. customthe methanol evaporated as more isopropanol
  27. additionwas added
  28. customOff-white crystals precipitated
  29. filtrationwere filtered
  30. customdried

Sources & evidence

ORD record
ord-a474d349464f457d9b092c5398573e42
Source dataset
uspto-grants-1993_12
Patent number
US05273993

Reaction notes

Loading…