A Quantitative Assay of Sodium Triacetoxyborohydride

Abstract

Sodium triacetoxyborohydride (STAB) is a common reducing agent with potency that degrades over time and is not uniformly assigned. A simple assay based on an aldehyde reduction has been developed to determine the active borohydride content of this reagent. The HPLC assay yield of a salicylaldehyde reduction has been shown to accurately determine this potency and has been validated against the H 2 evolution method as well as yields obtained from a reductive amination. The use of these assay data to adjust the STAB charge as well to optimize a reductive amination has been demonstrated.

Development of a Kilogram-Scale Synthesis of a Key Ulevostinag Subunit Part II: An Electrophilic Approach to Fluorinated Nucleosides

“…The control of several additional parameters proved crucial to the optimization of diastereoselectivity including (1) elevated temperature (40 vs 0 °C), (2) increased dilution, favoring intramolecular hydride delivery, (3) pre-ageing STAB in MeCN/AcOH to eliminate lot-to-lot variability in potency, presumably by consuming various hydride impurities, and (4) addition mode, with the addition of i -Bu-2 to STAB being preferable to its inverse. In practice, treatment of i -Bu-2 with 3 equiv of pre-aged STAB in 11:5 MeCN/HOAc (16 L/kg) afforded 1 in 95% AY and 95:5 dr (Scheme ).…”

Practical Synthesis of Reactive Immuno-PET Linker-Chelator (1R,2R)-RESCA-TFP

“…Indeed, as shown in Scheme , the reductive amination of (1 R ,2 R )-1,2-diaminocyclohexane ( 3 , 99% ee) with methyl 2-(4-formylphenyl)­acetate 8 by employing NaBH­(OAc) 3 (2 equiv) as the reducing agent in EtOH at 50 °C provided compound 9 in 72% assay yield with various over-benzylated species identified as the major impurities. A silica gel column chromatographic purification resulted in 50% isolated yield of product 9 with substantial product loss (ca.…”

“…Unless otherwise noted all reactions were run under a nitrogen atmosphere. 1 H and 13 C nuclear magnetic resonance spectra were recorded on a Bruker Avance 300 MHz, Bruker Avance III 500 MHz, or Bruker Avance III 600 MHz NMR spectrometer at ambient temperature. Data for 1 H NMR were reported in ppm relative to residual DMSO (δ 2.50 ppm) or CDCl 3 (δ 7.26 ppm) as follows: chemical shift, multiplicity (br = broad signal, s = singlet, d = doublet, t = triplet, q = quartet, p = pentet, sept = septet, m = multiplet, ABq = AB quartet), coupling constants, and integration.…”

“…Data for 1 H NMR were reported in ppm relative to residual DMSO (δ 2.50 ppm) or CDCl 3 (δ 7.26 ppm) as follows: chemical shift, multiplicity (br = broad signal, s = singlet, d = doublet, t = triplet, q = quartet, p = pentet, sept = septet, m = multiplet, ABq = AB quartet), coupling constants, and integration. All 13 C NMR spectra are reported in ppm relative to residual DMSO (δ 39.52 ppm) or CDCl 3 (δ 77.5 ppm). High-resolution mass spectrometry (HRMS) data were acquired on a Thermo Scientific Orbitrap Fusion mass spectrometer.…”

“…The solvent was removed in vacuo, and the residue was purified by silica gel column chromatography (20% EtOAc in n-heptane) to afford 10 (400 g, 0.65 mol, 79% yield, 98 A% HPLC). 1 13 (11). To a solution of methyl ester 10 (353 g, 0.60 mol) in THF (3 L, 8 mL/g) at 0 °C was added 1 M aqueous KOH (67.5 g, 1.2 mol in 1.2 L H 2 O) while maintaining the internal temperature below 10 °C.…”