Application scheme of BEHT Triflate [B7082] with DIPEA [D1599] for nucleophilic substitution of alcohols (Nu-H: amine, carboxylic acid, thiol, halide, cyanide, azide) with product examples and Clopidogrel.

Mitsunobu Reagent for Substitution of Alcohols with Weakly Acidic Nucleophiles

November 3, 2026

BEHT Triflate (B7082) is a new, stable solid reagent for the Mitsunobu reaction¹). Its bench-stable, easy-to-handle form removes the need for dropwise addition of azo compounds, which simplifies the experimental procedure. BEHT Triflate can be applied to weakly acidic nucleophiles (pKa >11), such as primary and secondary amines, carboxylic acids and thiols. The SN2 mechanism gives stereo-inverted products from optically active alcohols with minimal loss of optical purity, and the reaction has been reported to scale up to 10 mmol and to be applied in pharmaceutical synthesis¹). In a TCI practical example, benzyl (S)-(-)-lactate was reacted with indoline in the presence of BEHT Triflate and N,N-Diisopropylethylamine (DIEA) in 1,2-dichloroethane at room temperature, giving benzyl (R)-2-(indolin-1-yl)propanoate in 54% yield¹).