Formaldehyde → HCID 68430386, compound

HRID 384138Notes

Reaction equation

HRID 384138 reaction equation
[CH3:1][C:2]1[CH:7]=[CH:6][N:5]=[C:4]([OH:8])[CH:3]=1.[CH2:9]=[O:10].[Cl-].[NH4+].I[CH:14]([CH3:16])[CH3:15]>C(Cl)(Cl)Cl.O1CCCC1.[Li+].CCC[CH2-].C(=O)([O-])[O-].[Ag+2]>[CH:14]([O:8][C:4]1[CH:3]=[C:2]([CH2:1][CH2:9][OH:10])[CH:7]=[CH:6][N:5]=1)([CH3:16])[CH3:15]

Participants

9

Reactant 4

HCID 712FormaldehydeHCID 6362Isopropyl iodideHCID 25517Ammonium ChlorideHCID 178428601HCID 178428601, compound

Product 1

HCID 68430386HCID 68430386, compound

Reagents, catalysts & solvents 4

HCID 178418647HCID 178418647, compoundCatalystHCID 6212ChloroformSolventHCID 8028TetrahydrofuranSolventHCID 61028n-Butyl lithiumSolvent

Procedure

To a solution of 4-methylpyridin-2-ol (1.0 g) in chloroform (10 ml), 1.37 ml of 2-iodopropane and 3.8 g of silver carbonate (II) were added, and the reaction solution was stirred at room temperature for 24 hours. The reaction solution was Celite-filtered, and the filtrate was distilled off under reduced pressure to afford a crude product as a yellow oil. To a solution of the crude product in tetrahydrofuran (8 ml), 7.2 ml of N-butyllithium (1.5M hexane solution) was added at −78° C., and the reaction solution was stirred at the same temperature for 30 minutes and then stirred at room temperature for 15 minutes. The reaction solution was recooled to −78° C., 324 mg of paraformaldehyde was added, and the reaction solution was stirred for 3 hours while increasing the temperature of the reaction solution to room temperature. To the reaction solution was added a saturated aqueous ammonium chloride solution, and the mixture was extracted with ethyl acetate. The combined organic layers were washed with a saturated saline solution and dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure, and the residue obtained was purified by silica gel column chromatography (eluent: hexane/ethyl acetate (98:2-50/50)) to afford the title compound as a yellow oil.

Workup

  1. filtrationThe reaction solution was Celite-filtered
  2. distillationthe filtrate was distilled off under reduced pressure
  3. customto afford a crude product as a yellow oil
  4. stirringthe reaction solution was stirred at the same temperature for 30 minutes
  5. stirringstirred at room temperature for 15 minutes
  6. customwas recooled to −78° C.
  7. stirringthe reaction solution was stirred for 3 hours
  8. temperaturewhile increasing the temperature of the reaction solution to room temperature
  9. extractionthe mixture was extracted with ethyl acetate
  10. washThe combined organic layers were washed with a saturated saline solution
  11. dry with materialdried over anhydrous sodium sulfate
  12. distillationThe solvent was distilled off under reduced pressure
  13. customthe residue obtained
  14. customwas purified by silica gel column chromatography (eluent: hexane/ethyl acetate (98:2-50/50))

Sources & evidence

ORD record
ord-2b496de2b21f43c0ba12a68c0d3bb000
Source dataset
uspto-grants-2013_02
Patent number
US08367708B2

Reaction notes

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