Aftobetin　is　a　non-invasive　diagnosis　of　Alzheimer′s　disease,　that　can　bind　with　aggregated　β-amyloid　peptide　in　eye′s　lenses,　used　for　early　diagnosis　of　Alzheimer′s　disease　in　a　rapid　and　painless　mode.　The　reported　synthesis　of　this　probe　fell　short　in　the　aspects　of　greenness　and　economy　due　to　the　involvement　of　toxic　Chromium(IV)　oxidant,　noble　palladium　catalyst,　elevated　reaction　temperature,　the　long　reaction　time　as　well　as　the　cumbersome　workup.　Herein,　a　holistic　optimization　of　the　synthetic　process　was　achieved　via　the　employment　of　flow　technology　and　heterogenous　photocatalysis.　Firstly,　the　integration　of　heterogenous　carbon　nitrides　photocatalysis　and　circulation　flow　technology　furnished　the　air　oxidation　of　alcohol　and　nickel　catalyzed　C−N　coupling　at　20　g　scale,　thus　avoiding　the　use　of　toxic　Chromium　and　precious　palladium　species　respectively.　Flow-intensified　esterification　between　acyl　chloride　and　alcohol,　just　taking　30　seconds　replaced　the　Steglich　esterification　of　6　hours,　also　avoiding　the　generation　of　difficult-to-remove　dicyclohexylurea.　Finally,　C−N　coupling,　esterification　and　Knoevenagel　condensation　were　telescoped　together,　thus　simplifying　the　reaction　workup.　This　fully-flow　protocol　led　to　the　on-demand　synthesis　of　eight　probes.　©　2024　Wiley-VCH　GmbH.