Water → Ethyl-[6-(1-methyl-piperidin-4-yloxy)-pyridin-2-yl]-amine

HRID 1822014Notes

Reaction equation

HRID 1822014 reaction equation
[H-].[H-].[H-].[H-].[Li+].[Al+3].[CH3:7][N:8]1[CH2:13][CH2:12][CH:11]([O:14][C:15]2[N:20]=[C:19]([NH:21][C:22](=O)[CH3:23])[CH:18]=[CH:17][CH:16]=2)[CH2:10][CH2:9]1.[OH-].[Na+].O>C1COCC1>[CH2:22]([NH:21][C:19]1[CH:18]=[CH:17][CH:16]=[C:15]([O:14][CH:11]2[CH2:12][CH2:13][N:8]([CH3:7])[CH2:9][CH2:10]2)[N:20]=1)[CH3:23]

Participants

6

Reactant 4

HCID 962WaterHCID 14798Sodium HydroxideHCID 21226445Aluminium lithium hydrideHCID 57893607N-[6-(1-Methyl-piperidin-4-yloxy)-pyridin-2-yl]-acetamide

Product 1

HCID 57893778Ethyl-[6-(1-methyl-piperidin-4-yloxy)-pyridin-2-yl]-amineYield 49.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Add LiAlH4 (108 mg, 2.85 mmol) to a solution of N-[6-(1-methyl-piperidin-4-yloxy)-pyridin-2-yl]-acetamide (preparation 73, 238 mg, 0.95 mmol) in THF (10 mL) and heat at reflux for 3 days. Quench the reaction with water, add 1N NaOH and water, stir for 30 min. Extract with methylene dichloride three times, combine the organic layers, dry over Na2SO4, filter and concentrate to give a residue. Chromatography (silica gel) eluting with 4% 2M NH3-methanol in methylene dichloride provides 110 mg (49%) of the title compound as a colorless oil: mass spectrum (ion spray): m/z=236.0 (M+1); 1H NMR (CDCl3, ppm): 7.34 (t, 1H), 6.00 (d, 1H), 5.90 (d, 1H), 4.95 (m, 1H), 4.30 (m, 1H), 3.26 (m, 2H), 2.73 (m, 2H), 2.31 (s, 3H), 2.29 (m, 2H), 2.02 (m, 2H), 1.84 (m, 2H), 1.25 (t, 3H).

Workup

  1. temperatureheat
  2. temperatureat reflux for 3 days
  3. customQuench
  4. customthe reaction with water
  5. extractionExtract with methylene dichloride three times
  6. dry with materialdry over Na2SO4
  7. filtrationfilter
  8. concentrationconcentrate
  9. customto give a residue
  10. washChromatography (silica gel) eluting with 4% 2M NH3-methanol in methylene dichloride

Sources & evidence

ORD record
ord-896de7462c3845098b8ab0c2904a2b25
Source dataset
uspto-grants-2009_10
Patent number
US07608629B2

Reaction notes

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