Synthesis of the thioglycolic acid side chain at 1-position
Reagents and conditions: a)15 eq. Br(CH2)nCOOR, 2 eq. DBU, DMF, microwave, 90 °C, 50–60 min, 51%; b) conc. HCl/dioxane (1:1, 20 mL/mmol), r.t., 1 ~ 12 h, 50–80%. c) Me2NCSCl, K2CO3, NMP, 50 °C, 2 h, 90%; d) NMP, microwave, 180 °C, 20 min., 72%; e) (i) 4 eq. KOH, CH3OH, inert conditions, r.t., 12 h; (ii) BrCH2COOC(CH3)3, r.t., 12 h, 86%; f) H-Cube: H2 (40 bar, 25 °C), Pd/C (10%), CH3OH, flow rate: 1 ml/min, 100%; g) (i) Pyridine, THF/H2O (4:1), 0 °C, (ii) thiophene-2-sulfonyl chloride, 0 °C → r.t., 4 h, 58%.