4-Bromopyridinium chloride → tert-Butyl 8-(pyridin-4-yl)-2,8-diazaspiro[4,5]decane-2-carboxylate

HRID 1253759Notes

Reaction equation

HRID 1253759 reaction equation
C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1.[CH2:47]1[C:51]2([CH2:56][CH2:55][NH:54][CH2:53][CH2:52]2)[CH2:50][CH2:49][N:48]1[C:57]([O:59][C:60]([CH3:63])([CH3:62])[CH3:61])=[O:58].Cl.Br[C:66]1[CH:71]=[CH:70][N:69]=[CH:68][CH:67]=1>C1(C)C=CC=CC=1.CC([O-])=O.CC([O-])=O.[Pd+2]>[C:60]([O:59][C:57]([N:48]1[CH2:49][CH2:50][C:51]2([CH2:52][CH2:53][N:54]([C:66]3[CH:71]=[CH:70][N:69]=[CH:68][CH:67]=3)[CH2:55][CH2:56]2)[CH2:47]1)=[O:58])([CH3:63])([CH3:62])[CH3:61]

Participants

6

Reactant 3

HCID 881004-Bromopyridinium chlorideHCID 634876Binap, (A+-)-HCID 34178604tert-Butyl 2,8-diazaspiro[4.5]decane-2-carboxylate

Product 1

HCID 59047377tert-Butyl 8-(pyridin-4-yl)-2,8-diazaspiro[4,5]decane-2-carboxylateYield 43.3%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 1140TolueneSolvent

Procedure

BINAP (293 mg, 0.47 mmol) and Pd(OAc)2 (317 mg, 1.4 mmol) was added to a mixture of tert-butyl 2,8-diazaspiro[4.5]decane-2-carboxylate (5.66 g, 23.6 mmol), 4-bromopyridine HCl (4.58 g, 23.6 mmol) and sodium tert-butylate (6.8 g, 70.8 mmol) in toluene and the reaction mixture was degassed under argon for 20 minutes and heated under reflux for 4 h. The mixture was then diluted with ethyl acetate, stirred for 15 minutes and filtered over Celite. The organic phase was washed with water and sat. NaCl solution, dried over sodium sulfate and concentrated under reduced pressure. The crude product was purified by column chromatography. Yield: 43.3%

Workup

  1. customthe reaction mixture was degassed under argon for 20 minutes
  2. temperatureheated
  3. temperatureunder reflux for 4 h
  4. additionThe mixture was then diluted with ethyl acetate
  5. filtrationfiltered over Celite
  6. washThe organic phase was washed with water and sat. NaCl solution
  7. dry with materialdried over sodium sulfate
  8. concentrationconcentrated under reduced pressure
  9. customThe crude product was purified by column chromatography

Sources & evidence

ORD record
ord-6dd11934b14c4021820553c4c117834d
Source dataset
uspto-grants-2013_06
Patent number
US08455475B2

Reaction notes

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