Continuous flow process for production of cationic lipids

A continuous flow process for producing a compound of general formula (I)

• wherein R1, R2 and R3 independently from each other represent —H, C1-24 alkyl, or C2-24 alkenyl;
• L represents C1-12 alkylene, C2-12 alkenylene, C2-12 alkynylene, C3-15 cycloalkylene, C3-15 cycloalkenylene, or —(CH2—O—CH2)1-6—;
• P represents C1-24 alkylene, C2-24 alkenylene, C2-24 alkynylene, or —(CH2)m—(CH2—O—CH2)1-6—(CH2)n—;
• X is selected from —H, —OR4, —CN, —C(O)OR4, —OC(O)OR4, and —NR4R5;
• R4 and R3 independently from each other are selected from —H or C1-12 alkyl;
• wherein m and n are integers independently selected from 0 and 1;
• the process comprising the following steps:
• A) providing a continuous flow of a solution comprising acid chloride (II) and diol compound (III);
• B) continuously producing a compound of formula (IV) from the continuous flow of the solution comprising acid chloride (II) and diol compound (III) in a continuous flow reactor in the absence of a base;
• C) combining the continuous flow of a solution containing the compound of formula (IV) with a continuous flow of a mixture comprising an oxidizing agent;
• D) continuously producing a compound of formula (V) from the combined continuous flow obtained in step C) in a continuous flow reactor;
• E) combining the continuous flow containing the compound of formula (V) obtained in step D) with a continuous flow of a solution comprising a reducing agent and with a continuous flow of a solution comprising an amine compound of formula (VI)
• X—P—NH2 (VI)
• F) continuously producing the compound of formula (I) from the combined continuous flow obtained in step E) in a continuous flow reactor.