Dimethylformamide → 5-[2-(1,3-Dioxolan-2-yl)ethoxy]-2,3-difluoropyridine

HRID 81639

Reaction equation

HRID 81639 reaction equation
C(=O)([O-])[O-].[Cs+].[Cs+].Br[CH2:8][CH2:9][CH:10]1[O:14][CH2:13][CH2:12][O:11]1.CN(C)C=O.[F:20][C:21]1[CH:22]=[C:23]([OH:28])[CH:24]=[N:25][C:26]=1[F:27]>O>[O:11]1[CH2:12][CH2:13][O:14][CH:10]1[CH2:9][CH2:8][O:28][C:23]1[CH:22]=[C:21]([F:20])[C:26]([F:27])=[N:25][CH:24]=1

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 10796Cesium carbonateHCID 877762-(2-Bromoethyl)-1,3-dioxolaneHCID 684308605,6-Difluoropyridin-3-ol

Product 1

HCID 684297625-[2-(1,3-Dioxolan-2-yl)ethoxy]-2,3-difluoropyridineYield 38.1%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
100 °C

Procedure

Cesium carbonate (33 g, 100 mmol) and 2-(2-bromoethyl)-1,3-dioxolane (12 g, 67 mmol) were added to an N,N-dimethylformamide suspension (30 ml) of 5,6-difluoropyridin-3-ol (8.8 g, 67 mmol), and stirred at 100° C. for 1 hour. The reaction solution was cooled to room temperature, water was added, and extracted with ethyl acetate. The organic layer was washed with saturated saline water, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (hexane:chloroform=1:1 to 0:1) to obtain 5-[2-(1,3-dioxolan-2-yl)ethoxy]-2,3-difluoropyridine (5.9 g, yield: 38%) as a pale yellow oil.

Workup

  1. temperatureThe reaction solution was cooled to room temperature
  2. extractionextracted with ethyl acetate
  3. washThe organic layer was washed with 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:chloroform=1:1 to 0:1)

Sources & evidence

ORD record
ord-9e72d3e1c42543f1aabdb607ad88b529
Source dataset
uspto-grants-2014_09
Patent number
US08846700B2

Linked notes

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