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

HRID 1808358Notes

Reaction equation

HRID 1808358 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 monitoring: conversion about 30-35%). A catalytic amount of sodium iodide was added, and the reaction mixture was stirred for 8 h at 80° C. (TLC monitoring). Methanol and NaHCO3 solution were added to the reaction mixture, and stirring was carried out for 20 min. The mixture was then extracted with ethyl acetate and again washed with NaHCO3 solution and cold water. The organic phase was dried (Na2SO4) and concentrated in vacuo. The resulting crude product 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 for 8 h at 80° C. (TLC monitoring)
  3. stirringstirring
  4. waitwas carried out for 20 min
  5. extractionThe mixture was then extracted with ethyl acetate
  6. washagain washed with NaHCO3 solution and cold water
  7. dry with materialThe organic phase was dried (Na2SO4)
  8. concentrationconcentrated in vacuo
  9. customThe resulting crude product was purified by column chromatography (silica gel, 70% ethyl acetate/hexane)

Sources & evidence

ORD record
ord-002300d75df94803a1a35545cca42759
Source dataset
uspto-grants-2013_01
Patent number
US08357717B2

Reaction notes

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