PTC excels in performing reactions with water sensitive compounds such as chloroformates that are often used as protecting groups (e.g., benzyl chloroformate for the CBz group). PTC also excels in performing reactions involving anions, including nucleophilic substitutions using inorganic nucleophiles or base-induced alkylations.
When performing consecutive reactions for protection and a subsequent nucleophilic reaction (including base-initiated alkylation), you should consider PTC for streamlining the process by catalyzing both reactions using a single solvent, a single phase-transfer catalyst and achieving high atomic efficiency across both steps.
For example, the May 2013 PTC Reaction of the Month describes the nucleophilic substitution of a CBz protected serine methyl ester. The precursor protection reaction was not described in the patent, but since they were performing the subsequent thiophenoxide reaction with PTC (TBAB, TBPB or Aliquat 336), they could have easily performed the protection with benzyl chloroformate with the phase-transfer catalyst already present and likely be able to use the same solvent as the substitution reaction. This may have enabled avoiding isolation of the intermediate which would reduce cycle time and handling losses.
Commercial quantities of benzyl chloroformate can be obtained from VanDeMark Chemicals that also happens to be the commercial supplier of HEG Cl phase-transfer catalyst for high temperature reactions.
If your company can benefit from achieving higher process performance in a shorter development time by having access to the best PTC expertise available, now contact Marc Halpern by E-mail to inquire about using phase-transfer catalysis to achieve low-cost high-performance green chemistry.
If you’re not sure if PTC can help your reaction, now fill out the form shown at http://phasetransfer.com/projectform.pdf and send it to Marc Halpern by fax at +1 856-222-1124 or by E-mail of a scanned copy. If we do not have a secrecy agreement already in place, please use “R-groups” instead of the exact chemical structures.
