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In the synthesis of N-ethoxycarbonyl L-proline methyl ester from L-proline and ethyl chloroformate, I dry the organic phase over sodium sulfate. Can I use calcium chloride instead of sodium sulfate? I searched for information and I found that calcium chloride can contain basic impurities such as $\ce{Ca(OH)2}$ and $\ce{CaCl(OH)}$. Does someone know if it is actually the case? If it would be correct I think that it cannot be used because the impurities can hydrolyse the ester.

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    $\begingroup$ Why you want to change the drying reagent? $\endgroup$ – Mathew Mahindaratne Aug 4 '20 at 15:58
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Similar to @MathewMahindaratne's comment: if you know the drying agent suits your needs well enough, keep it. In particular here, sodium sulfate is a neuter one (as is calcium sulfate, too) is a safe option because while drying the organic layer, the agent will neither protonate, nor deprotonate your product. Thus, if the protocol states $\ce{Na2SO4}$, stick to it.

This is in contrast to calcium chloride which not only will contain traces of calcium hydroxyde when taken from the jar, but upon contact with additional water (a.k.a. while drying your organic solution) will create new $\ce{Ca(OH)2}$ and thus is considered a basic (and potentially deprotonating) drying agent. Note, $\ce{MgSO4}$ is considered as an acidic drying agent. Using the wrong salt solutions or drying agents during the workup actually may cleave off (e.g., protecting) groups and thus complicate the isolation and purification of your product.

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Yes, theoretically speaking, you CAN use it (not that you should), but only with suitable organic solvent and it also depends on the grade of Calcium chloride you have. I'll try to keep my answer as short and precise as possible. Two things to consider, as I said before, are the grade of Calcium chloride and the organic solvent used.

• Calcium chloride can be contaminated with Calcium hydroxide etc. but samples from Sigma Aldrich are extremely pure, 99.9%. If your reagent is not that pure or you just want to be sure, you can do two things:

  1. Treat Calcium chloride with dilute Hydrochloric acid, it will convert any Calcium hydroxide to Calcium chloride, then crystallize it and grind the crystals and place in a dessicator at 30°C for 12hrs (time will vary with the amount of calcium chloride you are using). You can also use more sophisticated techniques like drying the Calcium chloride in presence of dry Chlorine gas.
  2. You can try these two more sophisticated methods of Calcium chloride purification: crystallization from aqueous solutions and joint precipitation of impurities from aqueous solutions onto inorganic collectors (hydrated Aluminium or Zirconium oxides).

• Now about organic solvents. It's insoluble in liquid Ammonia, Ethyl acetate and DMSO. It's sparingly soluble in Acetone. It's soluble in Alcohols and Water. If you are using one of the first four solvents, you are good with Calcium chloride otherwise, it's gonna cause some problem. Also, as others have pointed out, Calcium chloride can form Calcium hydroxide if your reagents includes Water. I hope I was able to help or at least guide you in the right direction. All the best.

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