1. To a solution of DMF (7 mL) containing 600 mg (3.23 mmol) of 4-chloro-2-nitrobenzaldehyde was added 559 mg (4.04 mmol) of potassium carbonate and 294 μL (3.23 mmol) of methyl thioglycolate sequentially at 0°C. The reaction mixture was stirred for 30 min. at 0°C followed by continued stirring at room temperature for 24 hours. The reaction mixture was stirred at 0°C for 30 minutes, followed by continued stirring at room temperature for 24 hours. Upon completion of the reaction, the mixture was poured into ice water, the precipitate was collected by filtration, and the precipitate was dissolved in ethyl acetate. The organic phase was dried over anhydrous magnesium sulfate and concentrated to give 630 mg (86% yield) of methyl 6-chlorobenzo[b]thiophene-2-carboxylate as a white solid.1H NMR (CDCl3, 300 MHz): δ 3.95 (s, 3H), 7.88 (dd, J = 8.6, 1.9 Hz, 1H), 7.79 (d, J = 8.6 Hz, 1H), 7.85 (d, J = 8.6 Hz, 1H), 7.79 (d, J = 8.6 Hz, 1H). 7.85 (d, J = 1.9 Hz, 1H), 8.02 (s, 1H).
2. 6.95 mL of aqueous 1N LiOH was added to a 630 mg (2.78 mmol) solution of methyl 6-chlorobenzo[b]thiophene-2-carboxylate in THF (5 mL), and the reaction mixture was stirred for 4 h at room temperature. Upon completion of the reaction, the pH was adjusted to 2-3 with 1N HCl and subsequently extracted with ethyl acetate. The organic phases were combined, washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated to give 579 mg (98% yield) of 6-chlorobenzo[b]thiophene-2-carboxylic acid as a white solid.MS (ISP): 211.0 (M-H)-.
3. 139 mg (0.65 mmol) of 6-chlorobenzo[b]thiophene-2-carboxylic acid was converted to 52 mg (0.14 mmol) of (6-chlorobenzo[b]thiophen-2-ylmethyl)-[2-(3,4-dichlorophenyl)ethyl]amine by reference to the method of Example S3 (Steps a to b), the product was a colorless liquid.MS (ISP): 370.0 (M+H )+.
![Methyl 6-chlorobenzo[b]thiophene-2-carboxylate](/StructureFile/ChemBookStructure22/GIF/CB9956809.gif)
