Adopting the first synthetic strategy, Surrey et al. in the year 1949 reported the first industrial scale protocol for the HCQ synthesis which is still under active use. However, this 3-step protocol offers a 35% overall yield and utilises phenol as solvent (requires significant handling care). Following similar approach, Blanley et al. reported the first multi-gram scale asymmetric synthesis of (R) and (S) enantiomers of HCQ involving chiral resolution of 2 using enantiopure mandelic acid. Chen et al. overcome the drawbacks of previous protocol by excluding the bases and utilizes protectiondeprotection strategy to minimize the formation of desmethylated HCQ as a side product. Later on, Min et al. introduce the synthesis of HCQ using the high-pressure technique at comparably lower temperature with low reaction time. Using a similar approach, Yu et al. reported a sustainable and high-yielding continuous-flow synthesis of HCQ. (Scheme 2A.) Irrespective of reaction conditions utilised for the first synthetic strategy, the availability of key intermediate 2 is critical to meet the global demand. The general approach for the synthesis of 2 involves the direct reductive amination of 5-(ethyl(2-hydroxyethyl)amino)pentan-2-one (4) in presence of ammonia or reduction of corresponding oxime (3) in a two-step procedure (Scheme 2B).