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TES protection

  • Page ID
    15020
  • Below is a standard procedure for the triethylsilyl (TES) protection of an alcohol.

    Using triethylsilyl chloride (TESCl)

    Procedure

    To an ice-cold (0 °C) solution of the alcohol (1 mmol) in DMF (2 mL, 0.5 M) under N2 is added imidazole (3 mmol). TESCl (2 mmol) is then added dropwise. After complete disappearance of the starting material by TLC, the reaction mixture is quenched by addition of water (1 mL), diluted with Et2O (10 mL) and the layers are separated. The organic layer is washed with water (10 x 3 mL) and brine (2 mL), dried (Na2SO4), filtered and concentrated under reduced pressure. The residue is purified by flash chromatography on silica gel.

    Notes:

    • if the reaction proceeds efficiently, the equivalents of TESCl/imidazole can be reduced to 1.1/1.5
    • if the reaction is sluggish, try slowly warming to rt after the addition of TESCl or use TESOTf instead of TESCl
    • DCM can usually be used instead of DMF, but the reaction is generally slower
    • Excess TESOH may be hard to remove as it does not stain by TLC. It can be removed by leaving on high vac overnight.

     

    Mechanism

    Using triethylsilyl trifluoromethanesulfonate (TESOTf)

    Procedure

    To a solution of the alcohol (1 mmol) in DCM (2 mL, 0.5 M) under N2 at -78 °C, is added dry 2,6-lutidine (1.5 mmol). TESOTf (1.1 mmol) is then added dropwise. After complete disappearance of the starting material by TLC, the reaction mixture is quenched by addition of sat. aq. NaHCO3 (2 mL), diluted with DCM (5 mL) and brought back to rt. The layers are separated and the aqueous layer is extracted with DCM (3 x 2 mL). The combined organic layers are washed with brine (2 mL), dried (Na2SO4), filtered and concentrated under reduced pressure. The residue is purified by flash chromatography on silica gel.

    Notes:

    • if the reaction is sluggish, the equivalents of TESOTf/2,6-lutidine can be increased to 2.0/3.0
    • if the reaction is sluggish, try slowly warming to -40 °C for a few hours, then to 0 °C or rt

    Mechanism

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