Cesium carbonate → 2-(Pyridin-4-yl)-2-aza-bicyclo[2.2.2]octan-3-one

HRID 1896292Notes

Reaction equation

HRID 1896292 reaction equation
[CH:1]12[CH2:8][CH2:7][CH:4]([CH2:5][CH2:6]1)[C:3](=[O:9])[NH:2]2.Cl.Br[C:12]1[CH:17]=[CH:16][N:15]=[CH:14][CH:13]=1.C([O-])([O-])=O.[Cs+].[Cs+].CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[N:15]1[CH:16]=[CH:17][C:12]([N:2]2[C:3](=[O:9])[CH:4]3[CH2:7][CH2:8][CH:1]2[CH2:6][CH2:5]3)=[CH:13][CH:14]=1

Participants

6

Reactant 4

HCID 10796Cesium carbonateHCID 881004-Bromopyridinium chlorideHCID 1378872-Azabicyclo(2.2.2)octan-3-oneHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)

Product 1

HCID 673826672-(Pyridin-4-yl)-2-aza-bicyclo[2.2.2]octan-3-oneYield 61.9%

Reagents, catalysts & solvents 1

HCID 178418397HCID 178418397, compoundCatalyst

Conditions

Temperature
125 °C

Procedure

A mixture of 2-azabicyclo[2.2.2]octan-3-one (0.6 g, 4.8 mmol), 4-bromopyridine hydrochloride (1.17 g, 5.76 mmol), Cs2CO3 (2.36 g, 7.20 mmol) and xantphos (0.22 g, 0.38 mmol) was purged with argon gas for 10 min. Tetrakis(triphenylphosphine)palladium (0) (0.22 g, 0.19 mmol) was added and degassed for another 10 min. The reaction mixture was heated at 125° C. for 3 h. The reaction mixture was cooled to room temperature and filtered. The filtrate was concentrated and dried under reduced pressure to afford the crude compound. Purification by column chromatography over neutral alumina using 0.5% MeOH in CHCl3 as eluent afforded 600 mg (61.9%) of 2-(pyridin-4-yl)-2-aza-bicyclo[2.2.2]octan-3-one as pale yellow solid.

Workup

  1. customwas purged with argon gas for 10 min
  2. customdegassed for another 10 min
  3. temperatureThe reaction mixture was cooled to room temperature
  4. filtrationfiltered
  5. concentrationThe filtrate was concentrated
  6. customdried under reduced pressure
  7. customto afford the crude compound
  8. customPurification by column chromatography over neutral alumina using 0.5% MeOH in CHCl3 as eluent

Sources & evidence

ORD record
ord-ce30ce45a04c43468aadbfe6ff9bca27
Source dataset
uspto-grants-2013_08
Patent number
US08518948B2

Reaction notes

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