Scheme 1.

First-generation continuous flow process, with five synthetic operations. Manual operations are indicated by circular icons: Q quenching, E extraction, SS solvent switch, F filtration, SR solvent removal. Conditions: Step 1: ethynyl magnesium bromide (1), THF, 40 °C, 40 min, 90 %; Step 2: 1:2:1 H₂SO₄/AcOH/Ac₂O, MeCN/AcOH, 30 °C, 7 min, 91 %; Step 3: KOH, 40:1 EtOH/H₂O, 120 °C, 50 min, 91 %; Step 4: O₃, CH₂Cl₂, 25 °C, 10 s, then solid-supported thiourea, 95 %; Step 5: HCl/AcOH/H₂O, 150 °C, 18 min, 94 %.