Cesium carbonate → tert-butyl N-[(3S)-1-(5-bromo-1-methyl-2-oxo-3-pyridyl)-3-piperidyl]carbamate

HRID 57946Notes

Reaction equation

HRID 57946 reaction equation
Br[C:2]1[C:3](=[O:10])[N:4]([CH3:9])[CH:5]=[C:6]([Br:8])[CH:7]=1.[NH:11]1[CH2:16][CH2:15][CH2:14][C@H:13]([NH:17][C:18](=[O:24])[O:19][C:20]([CH3:23])([CH3:22])[CH3:21])[CH2:12]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>O1CCOCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[Br:8][C:6]1[CH:7]=[C:2]([N:11]2[CH2:16][CH2:15][CH2:14][C@H:13]([NH:17][C:18](=[O:24])[O:19][C:20]([CH3:22])([CH3:21])[CH3:23])[CH2:12]2)[C:3](=[O:10])[N:4]([CH3:9])[CH:5]=1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 1514171tert-butyl N-[(3S)-piperidin-3-yl]carbamateHCID 36143503,5-Dibromo-1-methylpyridin-2(1H)-one

Product 1

HCID 86707131tert-butyl N-[(3S)-1-(5-bromo-1-methyl-2-oxo-3-pyridyl)-3-piperidyl]carbamateYield 59.4%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
110 °C

Procedure

A mixture of 3,5-dibromo-1-methyl-pyridin-2-one (2.000 mmol; 533.8 mg), tert-butyl N-[(3S)-3-piperidyl]carbamate (2.00 mmol; 401 mg), cesium carbonate (4.0 mmol; 1303 mg), Xantphos (0.3400 mmol; 202.8 mg), and tris(dibenzylideneacetone)dipalladium(0) (0.2000 mmol; 185.0 mg) in 1,4-Dioxane (10 mL) was purged with Argon, then sealed and stirred at 110° C. overnight. The mixture was cooled to room temperature and filtered through Celite. The filtrate was concentrated and the residue was purified on silica eluted with 0 to 100% EtOAc in Heptane to afford tert-butyl N-[(3S)-1-(5-bromo-1-methyl-2-oxo-3-pyridyl)-3-piperidyl]carbamate as a yellow solid (458.6 mg, 59%).

Workup

  1. customwas purged with Argon
  2. customsealed
  3. temperatureThe mixture was cooled to room temperature
  4. filtrationfiltered through Celite
  5. concentrationThe filtrate was concentrated
  6. customthe residue was purified on silica
  7. washeluted with 0 to 100% EtOAc in Heptane

Sources & evidence

ORD record
ord-02ec5b27673a4a4e92c7a0ba42499636
Source dataset
uspto-grants-2016_09
Patent number
US09434725B2

Reaction notes

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