Formaldehyde → HCID 45097725, compound

HRID 1822054Notes

Reaction equation

HRID 1822054 reaction equation
[CH3:1][O-].[Na+].C=O.[CH3:6][N:7]1[CH2:12][CH2:11][CH:10]([O:13][C:14]2[N:19]=[C:18]([NH2:20])[CH:17]=[CH:16][CH:15]=2)[CH2:9][CH2:8]1.[BH4-].[Na+].[OH-].[K+]>CO>[CH3:1][NH:20][C:18]1[CH:17]=[CH:16][CH:15]=[C:14]([O:13][CH:10]2[CH2:9][CH2:8][N:7]([CH3:6])[CH2:12][CH2:11]2)[N:19]=1

Participants

7

Reactant 5

HCID 712FormaldehydeHCID 14797Potassium HydroxideHCID 4311764Sodium borohydrideHCID 10942334Sodium MethoxideHCID 187718666-(1-Methyl-piperidin-4-yloxy)-pyridin-2-ylamine

Product 1

HCID 45097725HCID 45097725, compoundYield 83.1%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

Combine sodium methoxide (290 mg, 5.38 mmol), paraformaldehyde (94 mg, 3.13 mmol), 6-(1-methyl-piperidin-4-yloxy)-pyridin-2-ylamine (preparation 60, 260 mg, 1.25 mmol) and methanol (5 mL), heat at 50° C. for 20 hr. Add NaBH4 (85 mg, 2.25 mmol), beat at reflux for 1.5 hr. Then add 1.0N KOH solution (2 mL), beat at reflux for 2 hr. Partition between water and CH2Cl2, extract aqueous phase with CH2Cl2. Combine organic layers, dry over Na2SO4, filter and concentrate to give a residue. Chromatography (silica gel) eluting with 5% 2M NH3-methanol in methylene dichloride provides 230 mg of methyl-[6-(1-methyl-piperidin-4-yloxy)-pyridin-2-yl]-amine with a small amount (5-10%) of inseparable starting amine.

Workup

  1. temperatureat reflux for 1.5 hr
  2. temperatureat reflux for 2 hr
  3. customPartition between water and CH2Cl2
  4. extractionextract aqueous phase with CH2Cl2
  5. dry with materialCombine organic layers, dry over Na2SO4
  6. filtrationfilter
  7. concentrationconcentrate
  8. customto give a residue
  9. washChromatography (silica gel) eluting with 5% 2M NH3-methanol in methylene dichloride

Sources & evidence

ORD record
ord-aa30c36199c54e43ba5310657f62dab6
Source dataset
uspto-grants-2009_10
Patent number
US07608629B2

Reaction notes

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