898566-17-1

1030825-20-7

898566-17-1

2-(5-bromo-2-methylbenzyl)-5-(4-fluorophenyl)thiophene (100 g; cf. WO 2005/012326) was dissolved in toluene (300 mL) at room temperature and under nitrogen atmosphere. To this solution, sodium iodide (83 g), cuprous(I) iodide (2.64 g), N,N'-dimethylethylenediamine (2.94 mL) and diethylene glycol dimethyl ether (50 mL) were added sequentially. The reaction mixture was heated to reflux temperature and stirred continuously for 36 hours. Upon completion of the reaction, ethyl acetate (300 mL) was added to the mixture at 40 °C and filtered through a filter pre-coated with activated carbon. The filtrate was washed and concentrated. The resulting residue was suspended in methanol (426 mL) at reflux temperature for 75 minutes. Subsequently, the suspension was cooled to 25 °C and stirring was continued for 1 hour. The precipitate was collected by filtration, washed with methanol and dried under vacuum at 50 °C to afford 2-(5-iodo-2-methylbenzyl)-5-(4-fluorophenyl)thiophene (94.9 g) in white crystalline form. The mass spectrum (APCI) showed a m/z of 409 (M + H); the melting point was 109-110°C. The crystal was found to have the following properties.