Cesium carbonate → 3-[4-(5-Bromo-2-fluoro-benzyl)-phenoxy]-oxetane

HRID 659884Notes

Reaction equation

HRID 659884 reaction equation
[Br:1][C:2]1[CH:3]=[CH:4][C:5]([F:16])=[C:6]([CH:15]=1)[CH2:7][C:8]1[CH:13]=[CH:12][C:11]([OH:14])=[CH:10][CH:9]=1.C(=O)([O-])[O-].[Cs+].[Cs+].[O:23]1[CH2:26][CH:25](OS(C2C=CC(C)=CC=2)(=O)=O)[CH2:24]1>CN(C)C=O.[Cl-].[Na+].O>[Br:1][C:2]1[CH:3]=[CH:4][C:5]([F:16])=[C:6]([CH:15]=1)[CH2:7][C:8]1[CH:13]=[CH:12][C:11]([O:14][CH:25]2[CH2:26][O:23][CH2:24]2)=[CH:10][CH:9]=1

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 13153907Oxetan-3-yl 4-methylbenzene-1-sulfonateHCID 66583002HCID 66583002, compound

Product 1

HCID 666159473-[4-(5-Bromo-2-fluoro-benzyl)-phenoxy]-oxetaneYield 72.1%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 57417360Sodium chloride; waterSolvent

Conditions

Temperature
65 °C

Procedure

To a solution of 4-(5-bromo-2-fluoro-benzyl)-phenol (1.1 g, 3.9 mmol) and cesium carbonate (1.91 g, 5.87 mmol) in N,N-dimethylformamide (15.0 mL) at room temperature was added a solution of toluene-4-sulfonic acid oxetan-3-yl ester (1.34 g, 8.0 mmol) in N,N-dimethylformamide (10.0 mL). The reaction mixture was then stirred overnight at 65° C. After a total of 18 hours, the reaction mixture was cooled to room temperature, diluted with brine and extracted 3 times with ethyl acetate. The combined organic layers were washed twice with water and once with brine, dried over sodium sulfate, filtered, and concentrated under reduced pressure. The crude residue was purified by flash chromatography over silica gel eluting with a gradient of 0 to 30% ethyl acetate in heptane to afford 0.948 g (72% yield) of the desired product as a white solid.

Workup

  1. temperatureAfter a total of 18 hours, the reaction mixture was cooled to room temperature
  2. extractionextracted 3 times with ethyl acetate
  3. washThe combined organic layers were washed twice with water and once with brine
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe crude residue was purified by flash chromatography over silica gel eluting with a gradient of 0 to 30% ethyl acetate in heptane

Sources & evidence

ORD record
ord-5603987996a241ffa04eb00ae053cda5
Source dataset
uspto-grants-2011_12
Patent number
US08080580B2

Reaction notes

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