n-Butyl lithium (0.64ml, 1.2 mmol) was added drop wise to a solution of diisopropyl amine (0.25 mL, 1.5 mmol) in dry THF at -78°C under nitrogen atmosphere over a period of 5 minutes. The reaction mixture was stirred at -20°C for 30 minutes. To this was added 5-bromo-benzo[b]thiophene (200 mg, 0.938 mmol) in dry THF at -78°C, continued stirring for a further 30 minutes at -78°C, followed by the addition of N-chlorosuccinamide (225 mg, 1.68 mmol) in dry THF at -78°C. The resulting mixture was stirred at room temperature for 2 hours. The reaction was monitored by TLC (100% hexane). The reaction mixture was partitioned between ethyl acetate and saturated ammonium chloride. The organic layer was dried over sodium sulfate and concentrated to afford the crude product. Purification by column chromatography on silica gel (100% hexane) afforded the product. Preparation of Intermediate 4-Bromo-2,6-difluoro-benzaldehyde (I-26a): Using analogous reaction condition and reagents as described in Example 20 for the preparation of 1-20a above, 1-bromo-3,5-difluoro-benzene (2 g, 2.10.36 mmol) in THF was reacted with DMF (1.43 g,19.68 mmol), n-butyl lithium (1.56 ml, 12.4 mmol) and diisopropyl amine (0.57 mL, 15.5 mmol) to afford crude product. Purification by column chromatography on silica gel (2% ethyl acetate in hexane) afforded 1.35 g of the product (61% yield). 1H NMR (CDCl3, 300 MHz): δ 11.5-11.0 (s, 1H), 7.4-7.2 (dd, 2H).
