Benzyl Bromide → Dibenzyl ether

HRID 1993127Notes

Reaction equation

HRID 1993127 reaction equation
O.[C:2]1([CH3:12])[CH:7]=[CH:6][C:5](S(O)(=O)=O)=[CH:4][CH:3]=1.[CH2:13]1[CH2:17][O:16][CH2:15][CH2:14]1.[CH2:18](Br)[C:19]1C=CC=C[CH:20]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C=O)C.O(C(OC)(C)C)C>[CH2:12]([O:16][CH2:15][C:14]1[CH:13]=[CH:17][CH:20]=[CH:19][CH:18]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 7498Benzyl BromideHCID 8028TetrahydrofuranHCID 10796Cesium carbonateHCID 521998p-Toluenesulfonic acid monohydrate

Product 1

HCID 7657Dibenzyl ether

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 64952,2-DimethoxypropaneSolvent

Procedure

To a solution of compound 23.1 (1.8 g, 5.03 mmol) in DMF (6 mL) and 2,2-dimethoxyl propane (12 mL) was added p-toluenesulfonic acid monohydrate (0.095 g, 0.5 mmol). The resultant mixture was stirred at 65° C. for 3 h. The excess 2,2-dimethoxyl propane was slowly distilled. The reaction mixture was cooled to room temperature and charged with THF (50 mL), benzyl bromide (0.8 mL, 6.73 mmol) and cesium carbonate (2.0 g, 6.13 mmol). The resulted mixture was stirred at 65° C. for 16 h. The reaction was quenched with acetic acid aqueous solution (4%, 100 mL) at 0° C., and extracted with ethyl acetate. The organic phase was dried over magnesium sulfate and concentrated under reduced pressure. The residue was purified by chromatography on silica gel to afford desired mono protected compound 23.3 (1.21 g, 49%).

Workup

  1. distillationThe excess 2,2-dimethoxyl propane was slowly distilled
  2. customThe reaction was quenched with acetic acid aqueous solution (4%, 100 mL) at 0° C.
  3. extractionextracted with ethyl acetate
  4. dry with materialThe organic phase was dried over magnesium sulfate
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified by chromatography on silica gel
  7. customto afford desired

Sources & evidence

ORD record
ord-a1b8e4d4ce60457eadb4bddb2b80e46b
Source dataset
uspto-grants-2010_01
Patent number
US07649015B2

Reaction notes

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