Methyl iodide → 2-Isopropyl-3-methoxymethylpyrazolo[1,5-a]pyridine

HRID 483091Notes

Reaction equation

HRID 483091 reaction equation
[CH:1]([C:4]1[C:12]([CH:13]=[O:14])=[C:7]2[CH:8]=[CH:9][CH:10]=[CH:11][N:6]2[N:5]=1)([CH3:3])[CH3:2].[BH4-].[Na+].[H-].[Na+].[CH3:19]I.[Cl-].[NH4+]>CO.O1CCCC1>[CH:1]([C:4]1[C:12]([CH2:13][O:14][CH3:19])=[C:7]2[CH:8]=[CH:9][CH:10]=[CH:11][N:6]2[N:5]=1)([CH3:3])[CH3:2]

Participants

8

Reactant 5

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 4311764Sodium borohydrideHCID 143032672-Isopropylpyrazolo[1,5-a]pyridine-3-carbaldehyde

Product 1

HCID 202425232-Isopropyl-3-methoxymethylpyrazolo[1,5-a]pyridineYield 55.3%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

To a cold solution of 2.0 g of 2-isopropyl-3-formylpyrazolo[1,5-a]pyridine in 60 ml of methanol were added in small portions 2.0 g of sodium borohydride under cooling and stirring. The mixture was heated to reflux for 2 hours and after cooling, concentrated in vacuo. Water was added to the residue and the mixture was extracted with dichloromethane. The organic layer was dried over anhydrous sodium sulfate and concentrated to give an oily residue, weighing 2.2 g. The residue in 5 ml of dry tetrahydrofuran was added to a suspension of 1.53 g of sodium hydride (55% oil suspension) in 10 ml of dry tetrahydrofuran under stirring and cooling. The mixture was stirred at room temperature for 5 minutes and then at reflux temperature for 15 minutes. After cooled under ice-water, 5.0 g of methyl iodide were added to the mixture. The mixture was stirred at toom temperature for an hour, followed by addition of aqueous 20% ammonium chloride, and extracted with ether. The ether layer was washed with saturated brine, dried over anhydrous sodium sulfate and concentrated to dryness. The residue was subjected to silica gel column chromatography, eluted with dichloromethane, to give 1.2 g (55%) of the desired compound as pale yellow oil.

Workup

  1. temperatureunder cooling
  2. temperatureThe mixture was heated
  3. temperatureto reflux for 2 hours
  4. temperatureafter cooling
  5. concentrationconcentrated in vacuo
  6. additionWater was added to the residue
  7. extractionthe mixture was extracted with dichloromethane
  8. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  9. concentrationconcentrated
  10. customto give an oily residue
  11. stirringunder stirring
  12. temperaturecooling
  13. stirringThe mixture was stirred at room temperature for 5 minutes
  14. temperatureat reflux temperature for 15 minutes
  15. temperatureAfter cooled under ice-water
  16. stirringThe mixture was stirred at toom temperature for an hour
  17. extractionextracted with ether
  18. washThe ether layer was washed with saturated brine
  19. dry with materialdried over anhydrous sodium sulfate
  20. concentrationconcentrated to dryness
  21. washeluted with dichloromethane

Sources & evidence

ORD record
ord-11e86c66d93e4b70b46598bc83b2c963
Source dataset
uspto-grants-1986_03
Patent number
US04578392

Reaction notes

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