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A reaction general procedure is given as follows:

A mixture of 2-fluoro-5-iodo pyridine $(\pu{1.0 mmol})$, methyl acetoacetate $(\pu{3.0 mmol})$, $\ce{CuI}$ $(\pu{10 mol\%})$, $\ce{K3PO4}$ $(\pu{3.0 mmol})$, and alcohol additive $(\pu{3.0 mmol})$ in DMSO $(\pu{4 mL})$ was stirred in $\ce{N2}$ at $\pu{80 ^\circ C}$. After completion of the reaction, the mixture was quenched with diluted hydrochloride $(\pu{2 mL}, \ 2M)$, and the solution was extracted with ethyl acetate $(3 \times \pu{5 mL})$.

The product is methyl 2-(6-fluoro-3-pyridyl)acetate.

  • Since the product contains a pyridine ring, can I quench it with hydrochloride $(\pu{2 mL}, \ 2M)$?
  • What is the best reagent for quenching?
  • If I start with $\pu{200 mg}$ of 2-fluoro-5-iodo pyridine, how much quenching reagent do I need?
  • How can I remove the copper salt?
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    $\begingroup$ MW of 5-fluoro-2-iodopyridine is 223 so 1 mmol is 223 mg. Starting with 200mg is very close to the described procedure so no need to adjust the amount of HCl quench. Due to the presence of the 6-F the pyridine is less basic. $\endgroup$
    – Waylander
    Commented May 15 at 6:09
  • $\begingroup$ “ stirred in N2 at 80 ∘C”? $\endgroup$
    – Karsten ♦
    Commented May 15 at 13:02
  • $\begingroup$ Yes, I purged the flask with N2 and set the temperature to 80 °C. $\endgroup$
    – Ella
    Commented May 16 at 22:45
  • $\begingroup$ @Karsten Well, $\pu{4 mL}$ of DMSO are present as a solvent in addition to the liquid methyl acetoacetate. But since nitrogen gas doesn't form a blanket to cover a reaction mixture which argon would provide, the description «in an atmosphere of nitrogen» or "in N2 atmosphere" is not wrong (though it sounds a bit like cell culture incubators in biochemistry) ... $\endgroup$
    – Buttonwood
    Commented May 20 at 20:15
  • $\begingroup$ @Ella Does the reference/paper not include more detailed SI? Why can't a filtration across an already EtOAc wetted plug of celite be an option (I infer from Pd coupling reactions), e.g. in a bigger Pasteur pipette, or made of a test tube to remove the CuI for good? See e.g., the blog post of the Baran lab; at first it needs some training by a colleague, but then works well enough. $\endgroup$
    – Buttonwood
    Commented May 20 at 20:18

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