Scheme 2.

Preparation of iodinated compounds (R/S)-14 (5-iodo-D/L-TIC(OH)) and their ester analogs (R/S)-13. Reagents and conditions: (a) (i) HBr conc., 40 °C, 10 min, (ii) aq. formaldehyde (37–41%), 75 °C, 4 h; (b) (i) NaNO₃, H₂SO₄ conc., 0 °C, 5 min, (ii) NH₄OH conc., pH = 8; (c) SOCl₂, EtOH, reflux, 20 h; (d) NIS, TfOH, r.t., 7.5 h; (e) AcCl, Et₃N, CHCl₃, r.t., 4.5 h; (f) SnCl₂, EtOH, reflux, 1 h; (g) (i) aq. H₂SO₄ 0.5 M, H₂O, 100 °C, 10 min, (ii) NaNO₂, 0 °C, 30 min, (iii) urea, reflux, 30 min; (h) (i) HCl conc., reflux, 7 h, (ii) HCl conc., EtOH, 15 h, (iii) NaHCO₃ sat., pH = 8; (i) (i) HCl 6M, reflux, 4–4.5 h, (ii) aq. KHCO₃ 5%, pH = 6–7, 4 °C, 16 h.