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

HRID 81655Notes

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-1b97044502834551b1bd9cd63cc5a8e0
Source dataset: uspto-grants-2014_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08846700B2

Reaction notes

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