Benzo[b]thiophene-2-carboxylic acid, 7-amino-, methyl ester (9CI)

Synthesis

1. Methyl 7-nitrobenzo[b]thiophene-2-carboxylate (100 mg) and acetic acid (4 mL) were added to a round-bottomed flask and stirred until completely dissolved. 2. dissolve SnCl2-2H2O (10 eq.) in 1.5 mL of concentrated hydrochloric acid and slowly add dropwise to the above solution. 3. The reaction mixture was stirred at room temperature for 12 hours and the progress of the reaction was monitored by TLC. 4. Upon completion of the reaction, the excess acid was partially removed on a rotary evaporator. 5. The reaction mixture was transferred to a 250 mL flask, cooled to 0 °C in an ice bath, and neutralized to pH 7 by slow addition of saturated NaHCO3 solution. 6. pH was adjusted to 9 by addition of solid NaHCO3. 7. The reaction mixture was diluted with EtOAc and filtered through a diatomaceous earth pad to remove tin by-products, the diatomaceous earth pad was washed well with EtOAc. 8. The filtrate was transferred to a partition funnel to separate the organic and aqueous layers. 9. The aqueous layer was extracted twice with EtOAc and all organic layers were combined. 10. The organic layer was dried with anhydrous MgSO4, filtered and concentrated to give methyl 7-aminobenzo[b]thiophene-2-carboxylate in 100% yield.

References

[1] Patent: US2003/225053, 2003, A1. Location in patent: Page 27, 35, 36
[2] Patent: US2003/225053, 2003, A1. Location in patent: Page 28
[3] Journal of Medicinal Chemistry, 2007, vol. 50, # 17, p. 4016 - 4026