Methyl iodide → ethyl 7-methoxy-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole-5-carboxylate

HRID 1880362Notes

Reaction equation

HRID 1880362 reaction equation
[OH:1][C:2]1[CH:3]=[C:4]([C:17]([O:19][CH2:20][CH3:21])=[O:18])[CH:5]=[C:6]2[C:10]=1[N:9]([CH:11]1[CH2:16][CH2:15][CH2:14][CH2:13][O:12]1)[N:8]=[CH:7]2.[C:22]([O-])([O-])=O.[K+].[K+].IC>CC(C)=O>[CH3:22][O:1][C:2]1[CH:3]=[C:4]([C:17]([O:19][CH2:20][CH3:21])=[O:18])[CH:5]=[C:6]2[C:10]=1[N:9]([CH:11]1[CH2:16][CH2:15][CH2:14][CH2:13][O:12]1)[N:8]=[CH:7]2

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 11430Potassium CarbonateHCID 66920492Ethyl 7-hydroxy-1-tetrahydropyran-2-YL-indazole-5-carboxylate

Product 1

HCID 66920406ethyl 7-methoxy-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole-5-carboxylateYield 92%

Reagents, catalysts & solvents 1

HCID 180AcetoneSolvent

Procedure

To a solution of ethyl 7-hydroxy-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole-5-carboxylate (1.45 g, 5.0 mmol) in acetone (20 mL) containing K2CO3 (760 mg, 5.50 mmol) was added iodomethane (781 mg, 0.34 mL, 5.5 mmo). The mixture was heated at reflux under N2 overnight. The mixture was cooled to room temperature, filtered, evaporated and partitioned between EtOAc and water. The aqueous phase was extracted with additional EtOAc. The combined organic extracts were washed with saturated aqueous NaCl, dried over Na2SO4, filtered and concentrated to provide crude product. The crude material was purified by chromatography (Isco, 0-40% EtOAc/heptane) to provide material which was dried under high vacuum overnight to afford ethyl 7-methoxy-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole-5-carboxylate (1.40 g, 92%).

Workup

  1. temperatureThe mixture was heated
  2. temperatureat reflux under N2 overnight
  3. filtrationfiltered
  4. customevaporated
  5. custompartitioned between EtOAc and water
  6. extractionThe aqueous phase was extracted with additional EtOAc
  7. washThe combined organic extracts were washed with saturated aqueous NaCl
  8. dry with materialdried over Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customto provide crude product
  12. customThe crude material was purified by chromatography (Isco, 0-40% EtOAc/heptane)
  13. customto provide material which
  14. customwas dried under high vacuum overnight

Sources & evidence

ORD record
ord-be8145f0082545c3a098be7ec0e1471c
Source dataset
uspto-grants-2012_11
Patent number
US08318762B2

Reaction notes

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