Reaction #168837

Reaction equation

2-(3-Bromopropoxy)tetrahydro-2H-pyran

cesium carbonate

N,N-dimethylacetamide

5-chloro-6-fluoropyridin-3-ol

→

3-chloro-2-fluoro-5-[3-(tetrahydro-2H-pyran-2-yloxy)propoxy]pyridine

Yield 68.0%

Solvents

water

Conditions

Workup

1. 1
   workup.ADDITIONwas added
2. 2
   Extractionextracted with ethyl acetate
3. 3
   WashThe organic layer was washed with water and saturated saline water
4. 4
   Dryingdried over anhydrous sodium sulfate
5. 5
   Concentrationconcentrated under reduced pressure
6. 6
   OtherThe obtained residue was purified by amine-type silica gel column chromatography (Moritex NH, hexane:ethyl acetate=18:1 to 11:1)

Procedure

2-(3-Bromopropoxy)tetrahydro-2H-pyran (12.93 g, 57.9 mmol) and cesium carbonate (39.5 g, 121.0 mmol) were added to an N,N-dimethylacetamide solution (80 ml) of 5-chloro-6-fluoropyridin-3-ol (8.14 g, 55.2 mmol), and stirred overnight under a nitrogen atmosphere at 100° C. The reaction solution was cooled with ice, 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 amine-type silica gel column chromatography (Moritex NH, hexane:ethyl acetate=18:1 to 11:1) to obtain 3-chloro-2-fluoro-5-[3-(tetrahydro-2H-pyran-2-yloxy)propoxy]pyridine (10.84 g, yield: 68%) as a pale yellow oil.

Source