Deprotection of N-Boc Groups under Continuous-Flow High-Temperature Conditions

Abstract

The scope of thermolytic, N-Boc deprotection was studied on 26 compounds from the Pfizer compound library, representing a diverse set of structural moieties. Among these compounds, 12 substrates resulted in clean (≥95% product) deprotection, and an additional three compounds gave ≥90% product. The thermal de-Boc conditions were found to be compatible with a large number of functional groups. A combination of computational modeling, statistical analysis, and kinetic model fitting was used to support an initial, slow, and concerted proton transfer with release of isobutylene, followed by a rapid decarboxylation. A strong correlation was found to exist between the electrophilicity of the N-Boc carbonyl group and the reaction rate.

Leveraging Free Volume Manipulation to Improve the Membrane Separation Performance of Amine‐Functionalized PIM‐1

“…It is well known that carbamic acid intermediates or isocyanates in close proximity to ‐NH 2 groups can rapidly react to form urea bonds, as shown in Scheme S10. In the case of the thermal deprotection procedure used here, very high temperatures (i.e., 250 °C) can potentially provide enough energy to start radical‐mediated or concerted deprotection mechanisms [37] . Both features could allow for urea bond formation.…”

Periodic Mesoporous Organosilica Nanoparticles with BOC Group, towards HIFU Responsive Agents

“…Indeed, the electrophilicity of BOC has been shown to strongly influence the reaction rate and reactivity of the cleavage. [37] Therefore, the synthesis of precursor molecules possessing more electrophilic BOC groups can be considered. Another possibility is to introduce carboxylic acid functions in the PMONPs using triethoxysilanes possessing this function [38] during the sol-gel procedure, in order to facilitate BOC cleavage in the materials.…”

Leveraging Free Volume Manipulation to Improve the Membrane Separation Performance of Amine‐Functionalized PIM‐1

“…In the case of the thermal deprotection procedure used here,very high temperatures (i.e., 250 8 8C) can potentially provide enough energy to start radical-mediated or concerted deprotection mechanisms. [37] Both features could allow for urea bond formation. In contrast, the acid deprotection was performed by soaking the film in adichloromethane non-solvent.…”

“…PIM-deBOC(thermal), however, displayed areduction of intensity of the three 13 C-NMR signals associated with -NH 2 and the appearance of an ew signal at ac hemical shift of 159 ppm (peak 4b), which was distinct from the -t-BOC carbonyl signal present at 155 ppm. Theo rigin of this new chemical signal was evaluated by comparing with spectra of -t-BOC and urea structural analogues and investigating possible deprotection mechanisms, [37,38] which are shown in Schemes S7-9 of the Supporting Information. It is well known that carbamic acid intermediates or isocyanates in close proximity to -NH 2 groups can rapidly react to form urea bonds,asshown in Scheme S10.…”