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

HRID 1253673Notes

Reaction equation

HRID 1253673 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 min. 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 approx. 30-35%). A catalytic amount of sodium iodide was added and the reaction mixture was stirred at 80° C. for 8 h (TLC control). Methanol and NaHCO3 solution was added to the reaction mixture and the mixture was stirred for 20 min. It was then extracted with ethyl acetate and the extract was washed again with NaHCO3 solution and cold water. The organic phase was dried (Na2SO4) and concentrated in vacuo. The crude product obtained in this way was purified by column chromatography (silica gel, 70% ethyl acetate/hexane). Yield: 1.0 g (40%)

Workup

  1. additionwas then added slowly
  2. stirringthe reaction mixture was stirred at 80° C. for 8 h (TLC control)
  3. stirringthe mixture was stirred for 20 min
  4. extractionIt was then extracted with ethyl acetate
  5. washthe extract was washed again with NaHCO3 solution and cold water
  6. dry with materialThe organic phase was dried (Na2SO4)
  7. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-772d4260b4e04715a5cb4b3487cae2af
Source dataset
uspto-grants-2013_06
Patent number
US08455475B2

Reaction notes

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