Hydrochloric Acid → 3-(4-(5-Bromo-2-chlorobenzyl)phenoxy)oxetane

HRID 659886Notes

Reaction equation

HRID 659886 reaction equation
[Br:1][C:2]1[CH:3]=[CH:4][C:5]([Cl: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.Cl>CN(C)C=O.C(OCC)(=O)C.O>[Br:1][C:2]1[CH:3]=[CH:4][C:5]([Cl: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

8

Reactant 4

HCID 313Hydrochloric AcidHCID 10796Cesium carbonate2×HCID 13153907Oxetan-3-yl 4-methylbenzene-1-sulfonateHCID 574237514-((5-Bromo-2-chlorophenyl)methyl)phenol

Product 1

HCID 666159483-(4-(5-Bromo-2-chlorobenzyl)phenoxy)oxetaneYield 70.7%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
120 °C

Procedure

To a solution of crude 4-(5-bromo-2-chlorobenzyl)phenol (3.0 g, 10 mmol) and cesium carbonate (4.9 g, 15 mmol) in N,N-dimethylformamide (77.5 mL) at room temperature was added a solution of toluene-4-sulfonic acid oxetan-3-yl ester (3.5 g, 15 mmol) in N,N-dimethylformamide (8 mL). The mixture was heated to 65° C. for 22 hours whereupon an additional aliquot of cesium carbonate (3.3 g, 10 mmol) was added. The reaction mixture was stirred for a further 12 hours at 120° C., cooled to room temperature whereupon water and ethyl acetate were added and the mixture was carefully acidified with 1N aqueous hydrochloric acid solution. The organic layer was separated, washed with brine (3 times), and concentrated in vacuo. Purification via Biotage MPLC (silica gel, eluting with a gradient of 0 to 25% ethyl acetate in heptane) afforded 3-(4-(5-bromo-2-chlorobenzyl)phenoxy)oxetane (2.5 g, 70% yield) as a white solid.

Workup

  1. additionwas added
  2. additionwere added
  3. customThe organic layer was separated
  4. washwashed with brine (3 times)
  5. concentrationconcentrated in vacuo
  6. customPurification via Biotage MPLC (silica gel
  7. washeluting with a gradient of 0 to 25% ethyl acetate in heptane)

Sources & evidence

ORD record
ord-a927ed7a8da44aa2a71216a555ccf789
Source dataset
uspto-grants-2011_12
Patent number
US08080580B2

Reaction notes

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