Scheme 2.

Routes to 4-Bromo-3-methyl-2-thiopheneacid Chloride, 1, From 3-Methylthiophene, 4. (a) NBS/AcOH, 64%; (b) Pd(OAc)₂/DPPP, Na₂CO₃, abs EtOH, 33 bar CO; or Mg turnings, THF, then dimethylcarbonate; (c) Br₂/AcOH, NaOH; 60°C; then Zn dust, 85°C; (d) NaOH,/H₂O, 91%; (e) MeMgBr (3M in ether), 1,2-DME, 50°C, 5 hr; CO₂ gas, 5°C; or 10% Pd/C/DPPP cat., Et₃N/H₂O, 34 bar CO pressure, 100°C, 59 h; (f) SOCl₂, cat. DMF, 1,2-DCE, 80°C; (g) NaOH/EtOH; (h) NH₃/H₂O; (i) POCl₃; (j) Br₂/DMF, 60°C; (k) NaOH/EtOH/H₂O; (l) Zn dust, AcOH, 100°C; (m) MeOH (to 12a)