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A Simple Homemade Reaction Station for use in Parallel Solution-Phase Synthesis. Optimization of a Regioselective One-Step Deprotective o-formylation Reaction Mediated by the Vilsmeier-Haack Reagent POCl3⋅DMF

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Summary

We report herein the fabrication of a simple and price-affordable portable reaction station for use in parallel solution-phase synthesis. This homemade device uses currently available laboratory components and equipment. Specifically designed to fit standard magnetic hotplates/stirrers, it can simultaneously hold up to 24 heated and magnetically stirred glass reactors of both 10 and 50 mL capacities. Glass reactors are connected by flexible 16-gauge metal needles to a central gas manifold equipped with an inlet/outlet for vacuum and inert gases. Reaction temperatures can be optimally varied from −78 ∘C to 150 ∘C. Using a statistical screening DOE method, this parallel array reactor station has been successfully operated to optimize the one-step deprotective O-formylation of a sterically hindered bis-O-tert-butyldiphenylsilyl (O-TBDPS) aromatic diol. The latter transformation was mediated by the Vilsmeier-Haack reagent POCl3⋅DMF using a range of Lewis acid and metal salt promoters, including their binary combinations.

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Abbreviations

DCE:

1,2-dichloroethane

DMF:

N, N-dimethylformamide

DOE:

design of experiments

HPLC:

high performance liquid chromatography

PMRS:

practical manual reaction station

PTFE:

polytetrafluoroethylene

PVC:

polyvinyl chloride

TBDMS:

tert-butyldimethylsilyl

TBDPS:

tert-butyldiphenylsilyl

TES:

triethylsilyl

Tf2O:

Trifluoromethanesulfonic anhydride

TMSOTf:

Trimethylsilyl trifluoromethanesulfonate

UV:

ultraviolet

VH:

Vilsmeier-Haack

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Authors and Affiliations

  1. Department of Chemistry, Bar-Ilan University, Ramat-Gan, 52900, Israel

    Vadim Kotlyar, Lior Shahar & J.-P. Lellouche (Prof.)

Authors
  1. Vadim Kotlyar
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  2. Lior Shahar
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  3. J.-P. Lellouche
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Correspondence to J.-P. Lellouche.

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Kotlyar, V., Shahar, L. & Lellouche, JP. A Simple Homemade Reaction Station for use in Parallel Solution-Phase Synthesis. Optimization of a Regioselective One-Step Deprotective o-formylation Reaction Mediated by the Vilsmeier-Haack Reagent POCl3⋅DMF. Mol Divers 10, 255–264 (2006). https://doi.org/10.1007/s11030-005-9013-1

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  • DOI: https://doi.org/10.1007/s11030-005-9013-1

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