（来源：康龙化成）

A Mild Boc Deprotection Using Armstrong’s Acid

Bijan Mirabi,* Byung Joo Lee, and Annie R. Hooper

Centralized Organic Synthesis Group, Small Molecule Therapeutic & Platform Technologies, AbbVie Inc., North Chicago, Illinois 60044, United States.

—J. Org. Chem. 2026, doi: org/10.1021/acs.joc.6c00963.

Recommended by Bingbing Chang_MC5

KEY WORDS: Boc deprotection (反应类型), N–H (成键类型), N-Boc amines (原料), ammonium disulfonate salt (产物), Armstrong’s acid (其他)

ABSTRACT: Naphthalene-1,5-disulfonic acid, or Armstrong’s acid, is demonstrated to be a reliable reagent in the mild deprotection of tert-butyl carbamate (Boc) protecting groups. This method is operationally simple and affords the deprotected amines as the corresponding disulfonate salts in up to quantitative yields. The reaction is mild and enables efficient deprotection in the presence of other sensitive functional groups. These salts are easily isolable via filtration from the reaction mixture and can be used as is in commonly employed reactions (i.e., reductive amination, amide coupling, Buchwald−Hartwig coupling). Additionally, they disclose the ammonium disulfonate salt as a bench-stable, non-hygroscopic source of ammonia.

Armstrong’s Acid and Its Use in Isolating Crystalline Material

Reaction Optimization for Boc Deprotection Mediated by Armstrong’s Acid

Comparison of Armstrong’s Acid to Standard Boc Deprotection Conditions

Substrate Scope

Synthetic Applications of Armstrong’s Acid Salts

Summary and Comments

Prof. Bijan Mirabi et al. have demonstrated the use of Armstrong’s acid, a commercially available and inexpensive organic acid, as a useful reagent for removing Boc protecting groups. The key features of the process are operational simplicity and chromatography-free isolation, where all products were isolated as easily handled and air-stable solids. The reaction generally displays high yields and good functional group tolerance, making it amenable for early- and late-stage synthesis campaigns. In addition, the product salts can be used as is in commonly used reactions of amines without requiring isolation of the parent amine via free basing. Although the methodology does not tolerate acid-sensitive functional groups, the use of Armstrong’s acid confers desirable physical properties which aid in storage and handling. They envision that this methodology will receive widespread adoption from medicinal and process chemists alike and can be used as an alternative to traditional deprotection conditions when the products prove difficult to handle or isolate.