This paper describes a synthesis of ALC‐0315 by a sequence that more than doubles the overall yield relative to the published one, and that employs much cleaner reactions, thereby facilitating purifications to a considerable extent
ALC‐ 0315 is a key component of the Pfizer‐BioNTech COVID‐ 19 vaccine and a highly sought‐after lipid for nucleic acid therapeutics research. This paper, a study in reductive amination, describes a synthetic route that more than doubles the overall yield relative to the published one. Key aspects of the work include the use of (i) a protected form of a poorly organic‐soluble aminoalcohol, (ii) a TEMPO/bleach oxidation to produce crucial aldehydes, and (iii) a more organic‐soluble triacyloxyborohydride reagent.