4-Toluenesulfonyl chloride → HCID 86587502, compound

HRID 985417Notes

Reaction equation

HRID 985417 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[C:9](=[O:15])[O:10][CH:11]([CH3:14])[C:12]=1O.O.[NH2:17][NH2:18].[S:19](Cl)([C:22]1[CH:28]=[CH:27][C:25]([CH3:26])=[CH:24][CH:23]=1)(=[O:21])=[O:20].C(N(CC)CC)C>C(O)C.ClCCl>[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[C:9]([O:15][S:19]([C:22]2[CH:28]=[CH:27][C:25]([CH3:26])=[CH:24][CH:23]=2)(=[O:21])=[O:20])=[N:17][NH:18][C:12]=1[CH:11]([OH:10])[CH3:14]

Participants

7

Reactant 4

HCID 73974-Toluenesulfonyl chlorideHCID 8471TriethylamineHCID 24654Hydrazine hydrate (1:1)4×HCID 54720229HCID 54720229, compound

Product 1

HCID 86587502HCID 86587502, compound

Reagents, catalysts & solvents 2

HCID 702EthanolSolvent2×HCID 6344DichloromethaneSolvent

Procedure

To 3-(2-fluorophenyl)-4-hydroxy-5-methyl-5H-furan-2-one (18.7 g, 90 mmol) in ethanol (90 ml) was added hydrazine hydrate (24 ml, 0.45 mol), and the mixture was stirred at reflux for 3 days. The solution was concentrated to approximately 30 ml, and was then stirred at 90° C. for 1 week. Hydrazine hydrate (24 ml, 0.45 mol) was added, and the mixture was stirred at 90° C. for another week. More hydrazine hydrate (24 ml, 0.45 mol) was added, and the solution was stirred as before for 1 week, and was then allowed to concentrate to approximately 30 mL Ethanol (90 ml) and hydrazine hydrate (24 ml, 0.45 mol) were added, and the mixture was heated at reflux for 1 week. The solvent was removed in vacuo, yielding a glassy foam. This was suspended in dichloromethane (200 ml) and tosyl chloride (20.4 g, 0.107 mol) and triethylamine (16.3 ml, 0.165 mol) were added at 5° C. The solution was allowed to warm to room temperature and was stirred overnight. The mixture was washed with saturated sodium chloride solution (1×100 ml), dried over magnesium sulfate, and was then concentrated in vacuo. The residue was purified by flash chromatography on silica gel (20 to 50% ethyl acetate in dichloromethane, UV detection), yielding toluene-4-sulfonic acid 4-(2-fluorophenyl)-5-(1-hydroxyethyl)-1H-pyrazol-3-yl ester as a yellow glass, which solidified upon standing (17.6 g). 1H NMR (400 MHz, CDCl3) δ 1.33 (3H, d, J=6.6 Hz), 2.38 (3H, s), 5.01 (1H, q, J=6.6 Hz), 6.98 (1H, m), 7.11 (3H, m), 7.27 (2H, m), 7.80 (2H, d, J=8.3 Hz), 10.30 (1H, br s); MS (ES+) m/e 377 [MH]+.

Workup

  1. temperatureat reflux for 3 days
  2. concentrationThe solution was concentrated to approximately 30 ml
  3. stirringwas then stirred at 90° C. for 1 week
  4. stirringthe mixture was stirred at 90° C. for another week
  5. stirringthe solution was stirred as before for 1 week
  6. additionwere added
  7. temperaturethe mixture was heated
  8. temperatureat reflux for 1 week
  9. customThe solvent was removed in vacuo
  10. customyielding a glassy foam
  11. stirringwas stirred overnight
  12. washThe mixture was washed with saturated sodium chloride solution (1×100 ml)
  13. dry with materialdried over magnesium sulfate
  14. concentrationwas then concentrated in vacuo
  15. customThe residue was purified by flash chromatography on silica gel (20 to 50% ethyl acetate in dichloromethane, UV detection)

Sources & evidence

ORD record
ord-39a41d4f103c49e093e92508c65350be
Source dataset
uspto-grants-2005_03
Patent number
US06872720B2

Reaction notes

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