Pyrazole → 1-(2-Tetrahydropyranyl)-1H-pyrazole

HRID 1530555Notes

Reaction equation

HRID 1530555 reaction equation
[NH:1]1[CH:5]=[CH:4][CH:3]=[N:2]1.[O:6]1[CH:11]=[CH:10][CH2:9][CH2:8][CH2:7]1.C(O)(C(F)(F)F)=O>[H-].[Na+]>[O:6]1[CH2:11][CH2:10][CH2:9][CH2:8][CH:7]1[N:1]1[CH:5]=[CH:4][CH:3]=[N:2]1

Participants

5

Reactant 3

HCID 1048PyrazoleHCID 6422Trifluoroacetic acidHCID 80803,4-dihydro-2H-pyran

Product 1

HCID 218663101-(2-Tetrahydropyranyl)-1H-pyrazoleYield 49.2%

Reagents, catalysts & solvents 1

HCID 24758Sodium hydrideCatalyst

Procedure

A mixture of 1H-pyrazole (6.00 g, 88.1 mmol), 3,4-dihydro-2H-pyran (9.00 g, 107 mmol), and TFA (cat. 2.00 mL) was heated to reflux for 5 hr. At the end of reaction, NaH (100 mg, 4.17 mmol) was added to quench the reaction. The resulting mixture was extracted with ethyl acetate, washed with brine, dried over MgSO4, filtered, and evaporated. The residue was purified by silica gel chromatography eluting with EtOAc/petroleum ether (1:100) to afford 1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazole (6.6 g, 49% yield) as pale yellow sold. LCMS (ESI) m/z: 153.1 [M+H+].

Workup

  1. temperaturewas heated
  2. temperatureto reflux for 5 hr
  3. additionwas added
  4. customto quench
  5. customthe reaction
  6. extractionThe resulting mixture was extracted with ethyl acetate
  7. washwashed with brine
  8. dry with materialdried over MgSO4
  9. filtrationfiltered
  10. customevaporated
  11. customThe residue was purified by silica gel chromatography
  12. washeluting with EtOAc/petroleum ether (1:100)

Sources & evidence

ORD record
ord-cec32b6268f342e7b751bc26314409d6
Source dataset
uspto-grants-2015_07
Patent number
US09090628B2

Reaction notes

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