Cesium carbonate → 6-(3-Fluoroazetidin-1-yl)-2-methyl-3-nitropyridine

HRID 510481Notes

Reaction equation

HRID 510481 reaction equation
Cl[C:2]1[N:7]=[C:6]([CH3:8])[C:5]([N+:9]([O-:11])=[O:10])=[CH:4][CH:3]=1.C([O-])([O-])=O.[Cs+].[Cs+].[F:18][CH:19]1[CH2:22][NH:21][CH2:20]1>CN(C=O)C.CCOC(C)=O>[F:18][CH:19]1[CH2:22][N:21]([C:2]2[N:7]=[C:6]([CH3:8])[C:5]([N+:9]([O-:11])=[O:10])=[CH:4][CH:3]=2)[CH2:20]1

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 2531236-Chloro-2-methyl-3-nitropyridineHCID 36035423-Fluoroazetidine

Product 1

HCID 895591516-(3-Fluoroazetidin-1-yl)-2-methyl-3-nitropyridineYield 98%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of 6-chloro-2-methyl-3-nitropyridine (0.5 g, 2.9 mmol) in DMF (5 mL) was added Cs2CO3 (1.9 g, 5.8 mmol) followed 3-fluoroazetidine (0.64 g, 5.8 mmol) and the reaction mixture was heated for 2 h at 80° C. The reaction mixture was then diluted with EtOAc and the organic layer was washed with saturated aqueous sodium bicarbonate solution. The organic layer was then dried over sodium sulphate and concentrated. The crude material obtained was purified by column chromatography (silica: 100-200 mesh, MeOH:DCM 2-3%) to afford the title compound (0.6 g, 92%). LCMS (ES+) 211.95 (M+H)+, RT 2.33 minutes (method 1).

Workup

  1. washthe organic layer was washed with saturated aqueous sodium bicarbonate solution
  2. dry with materialThe organic layer was then dried over sodium sulphate
  3. concentrationconcentrated
  4. customThe crude material obtained
  5. customwas purified by column chromatography (silica: 100-200 mesh, MeOH:DCM 2-3%)

Sources & evidence

ORD record
ord-091cf670ef17446db971cfd83348d3b7
Source dataset
uspto-grants-2015_08
Patent number
US09096614B2

Reaction notes

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