Dimethylformamide → 3-Chloro-5-(2,2-diethoxyethoxy)-2-fluoropyridine

HRID 1517285Notes

Reaction equation

HRID 1517285 reaction equation
[C:1](=O)([O-])[O-].[Cs+].[Cs+].BrC[CH2:9][CH:10]1O[CH2:13][CH2:12][O:11]1.CN(C)[CH:17]=[O:18].[Cl:20][C:21]1[CH:22]=[C:23]([OH:28])[CH:24]=[N:25][C:26]=1[F:27]>O>[Cl:20][C:21]1[C:26]([F:27])=[N:25][CH:24]=[C:23]([O:28][CH2:9][CH:10]([O:18][CH2:17][CH3:1])[O:11][CH2:12][CH3:13])[CH:22]=1

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 10796Cesium carbonateHCID 877762-(2-Bromoethyl)-1,3-dioxolaneHCID 224515553-Chloro-2-fluoro-5-hydroxypyridine

Product 1

HCID 684276023-Chloro-5-(2,2-diethoxyethoxy)-2-fluoropyridineYield 62%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
100 °C

Procedure

Cesium carbonate (2.9 g, 8.9 mmol) and 2-(2-bromoethyl)-1,3-dioxolane (990 mg, 5.0 mmol) were added to an N,N-dimethylformamide suspension (10 ml) of 5-chloro-6-fluoropyridin-3-ol (570 mg, 3.9 mmol), and stirred at 100° C. for 4 hours. The reaction solution was cooled to room temperature, water was added, and extracted with ethyl acetate. The organic layer was washed with water and saturated saline water, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (hexane:ethyl acetate=70:30) to obtain 3-chloro-5-(2,2-diethoxyethoxy)-2-fluoropyridine (640 mg, yield: 62%) as a colorless oil.

Workup

  1. temperatureThe reaction solution was cooled to room temperature
  2. extractionextracted with ethyl acetate
  3. washThe organic layer was washed with water and saturated saline water
  4. dry with materialdried over anhydrous sodium sulfate
  5. concentrationconcentrated under reduced pressure
  6. customThe obtained residue was purified by silica gel column chromatography (hexane:ethyl acetate=70:30)

Sources & evidence

ORD record
ord-f6f4165399634bf89e666a073b23b815
Source dataset
uspto-grants-2012_07
Patent number
US08232284B2

Reaction notes

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