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

HRID 1517294Notes

Reaction equation

Br[CH2:2][CH2:3][CH2:4][O:5][CH:6]1[CH2:11][CH2:10][CH2:9][CH2:8][O:7]1.C(=O)([O-])[O-].[Cs+].[Cs+].CN(C)C(=O)C.[Cl:24][C:25]1[CH:26]=[C:27]([OH:32])[CH:28]=[N:29][C:30]=1[F:31]>O>[Cl:24][C:25]1[C:30]([F:31])=[N:29][CH:28]=[C:27]([O:32][CH2:2][CH2:3][CH2:4][O:5][CH:6]2[CH2:11][CH2:10][CH2:9][CH2:8][O:7]2)[CH:26]=1

Participants

Conditions

Temperature: 100 °C

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.

Workup

additionwas added
extractionextracted with ethyl acetate
washThe organic layer was washed with water and saturated saline water
dry with materialdried over anhydrous sodium sulfate
concentrationconcentrated under reduced pressure
customThe obtained residue was purified by amine-type silica gel column chromatography (Moritex NH, hexane:ethyl acetate=18:1 to 11:1)

Sources & evidence

ORD record: ord-27116e4ea3774df6b0bf1b453808aa3d
Source dataset: uspto-grants-2012_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08232284B2

Reaction notes

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