Sodium Iodide → tert-Butyl 9-(pyridin-4-yloxy)-3-azaspiro[5.5]undecane-3-carboxylate

HRID 2387933Notes

Reaction equation

HRID 2387933 reaction equation
Cl.Cl[C:3]1[CH:8]=[CH:7][N:6]=[CH:5][CH:4]=1.[H-].[Na+].[OH:11][CH:12]1[CH2:29][CH2:28][C:15]2([CH2:20][CH2:19][N:18]([C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[CH2:17][CH2:16]2)[CH2:14][CH2:13]1.[I-].[Na+].C([O-])(O)=O.[Na+]>CS(C)=O.CO>[N:6]1[CH:7]=[CH:8][C:3]([O:11][CH:12]2[CH2:13][CH2:14][C:15]3([CH2:20][CH2:19][N:18]([C:21]([O:23][C:24]([CH3:25])([CH3:26])[CH3:27])=[O:22])[CH2:17][CH2:16]3)[CH2:28][CH2:29]2)=[CH:4][CH:5]=1

Participants

8

Reactant 5

HCID 5238Sodium IodideHCID 24758Sodium hydrideHCID 818524-Chloropyridine hydrochlorideHCID 516892Sodium BicarbonateHCID 66701044tert-Butyl 9-hydroxy-3-azaspiro[5.5]undecane-3-carboxylate

Product 1

HCID 66701182tert-Butyl 9-(pyridin-4-yloxy)-3-azaspiro[5.5]undecane-3-carboxylate

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolvent2×HCID 887MethanolSolvent

Procedure

4-Chloropyridine hydrochloride (1.3 g) was added to sodium hydride (0.89 g) in DMSO (20 ml), and the mixture was stirred for 10 minutes. tert-Butyl 9-hydroxy-3-azaspiro[5.5]undecane-3-carboxylate (2.0 g) in DMSO (20 ml) was then added slowly, and the mixture was stirred overnight (TLC control, conversion about 30-35%). A catalytic amount of sodium iodide was added, and the reaction mixture was stirred for 8 hours at 80° C. (TLC monitoring). Methanol and NaHCO3 solution were added to the reaction mixture, and stirring was carried out for 20 minutes. The mixture was then extracted with ethyl acetate and washed again with NaHCO3 solution and cold water. The organic phase was dried (Na2SO4) and concentrated in vacuo. The crude product so obtained was purified by column chromatography (silica gel, 70% ethyl acetate/hexane). Yield: 1.0 g (40%)

Workup

  1. stirringthe mixture was stirred overnight (TLC control, conversion about 30-35%)
  2. stirringthe reaction mixture was stirred for 8 hours at 80° C. (TLC monitoring)
  3. stirringstirring
  4. waitwas carried out for 20 minutes
  5. extractionThe mixture was then extracted with ethyl acetate
  6. washwashed again with NaHCO3 solution and cold water
  7. dry with materialThe organic phase was dried (Na2SO4)
  8. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-69307e941f5e472a84cca7d2c18850c8
Source dataset
uspto-grants-2012_09
Patent number
US08269000B2

Reaction notes

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