p-Toluenesulfonic acid → HCID 11010272, compound

HRID 1634095Notes

Reaction equation

HRID 1634095 reaction equation
O1CCCCC1[O:7][CH2:8][C:9]1[CH:13]=[C:12]([CH2:14][CH3:15])[NH:11][N:10]=1.C(O[K])(C)(C)C.F[C:23]1[CH:28]=[CH:27][C:26]([N+:29]([O-:31])=[O:30])=[CH:25][CH:24]=1.C1(C)C=CC(S(O)(=O)=O)=CC=1>C1COCC1.O.CO>[N+:29]([C:26]1[CH:27]=[CH:28][C:23]([N:11]2[C:12]([CH2:14][CH3:15])=[CH:13][C:9]([CH2:8][OH:7])=[N:10]2)=[CH:24][CH:25]=1)([O-:31])=[O:30]

Participants

8

Reactant 4

HCID 6101p-Toluenesulfonic acidHCID 9590p-FluoronitrobenzeneHCID 178418922HCID 178418922, compoundHCID 178436642HCID 178436642, compound

Product 1

HCID 11010272HCID 11010272, compoundYield 48.5%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 3-(tetrahydropyran-2-yloxy)methyl-5-ethylpyrazole (27.0 g, 0.13 mol) in dry THF (250 mL) was added tert-BuOK (14.4g, 0.13 mol) under nitrogen. After 10 min, 4-fluoronitrobenzene (18.1 g, 0.13 mol) was added. The mixture was heated to reflux for 10 hr, the solvent was then removed under vacuum The residue was taken up in ethyl acetate and washed with water, The organic layer was dried over MgSO4 and filtered. The filtrate was treated with active carbon (3.0 g, norit A alkaline) at reflux for 10 min and filtered through a pad of diatomaceous earth. The filtrate was concentrated to give a crude 7:1 mixture of regioisomers, which was dissolved in a 101: mixture of methanol and water (175 mL) and p-toluenesulfonic acid (1.2 g, 6.4 mmol) was added. The solution was stirred at room temperature for 12 hours and concentrated. The residue was taken up in ethyl acetate and washed with water. The organic layer was dried over MgSO4, filtered and concentrated to a crude solid. Recrystallization in a 1:1 mixture of hexane and ethyl acetate gave the title compound (15.6 g, 45%). mp: 151-152° C.

Workup

  1. temperatureThe mixture was heated
  2. temperatureto reflux for 10 hr
  3. customthe solvent was then removed under vacuum The residue
  4. washwashed with water
  5. dry with materialThe organic layer was dried over MgSO4
  6. filtrationfiltered
  7. additionThe filtrate was treated with active carbon (3.0 g, norit A alkaline)
  8. temperatureat reflux for 10 min
  9. filtrationfiltered through a pad of diatomaceous earth
  10. concentrationThe filtrate was concentrated
  11. customto give
  12. additiona crude 7:1 mixture of regioisomers, which
  13. dissolutionwas dissolved in a 101
  14. additionwas added
  15. concentrationconcentrated
  16. washwashed with water
  17. dry with materialThe organic layer was dried over MgSO4
  18. filtrationfiltered
  19. concentrationconcentrated to a crude solid
  20. customRecrystallization
  21. additionin a 1:1 mixture of hexane and ethyl acetate

Sources & evidence

ORD record
ord-d1c0f5ee0eb040049953e4ef77539a74
Source dataset
uspto-grants-2003_01
Patent number
US06506747B1

Reaction notes

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