An Efficient Synthesis of Solriamfetol Hydrochloride Substantially Free From Impurities: Identification, Synthesis, and Characterization of Novel Impurities

ABSTRACT An improved, novel, and efficient three‐step synthetic process for the production of solriamfetol hydrochloride ( 1 ), an anti‐narcolepsy medication designed to address excessive daytime sleepiness, has been disclosed. This method achieves an overall yield of 82% and demonstrates purity exceeding 99.95%, as confirmed by HPLC analysis. The superlative reaction conditions were identified by assessing the impurity profile and its formation during the synthesis. Six significant process‐related impurities were identified and characterized, with optimizations resulting in a reduction of impurity levels below 0.05%, thereby ensuring compliance with ICH guidelines (ICH Q3A/B guidelines). The improved three‐step synthetic protocol for Solriamfetol hydrochloride, substantially free from impurities, employs milder reaction conditions, a shorter cycle time, and the use of non‐hazardous reagents, resulting in enhanced process safety. The developed synthesis method is robust, cost‐effective, reproducible, and suitable for commercial production. The high purity (HPLC purity: 99.95%) of the final Solriamfetol hydrochloride (API) enhances product safety by minimizing potential impurities to meet a regulatory‐compliant approach for the large‐scale manufacture of Solriamfetol hydrochloride with improved quality and consistency.