3-AMINO-2-BROMO-BENZOIC ACID METHYL ESTER

Uses

Methyl 3-Amino-2-bromobenzoate is used in preparation of Carbazole-based compounds and its application as IDO inhibitor.

Synthesis

Methyl 2-bromo-3-nitrobenzoate (12.9 g, 49.5 mmol) was used as feedstock and prepared according to the method described by Webber ES et al. (Patent Application No. WO 01/16136 A2). The feedstock was refluxed with SnCl2 (42 g, 223 mmol) in a mixed solution of methanol (225 mL, 0.2 M) and H2O (5.3 g, 243 mmol) for 2 hours. After completion of the reaction, it was cooled to room temperature and diatomaceous earth (20 g) and dichloromethane (1 L) were added, followed by the slow addition of 3 N aqueous sodium hydroxide solution (150 mL) under vigorous stirring. The reaction mixture was filtered and the organic phase was washed with saturated aqueous sodium chloride solution. The organic layer was dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure to remove all volatiles to afford the intermediate methyl 3-amino-2-bromobenzoate (11.4 g) in 98% yield.1H-NMR (d6-DMSO) δ: 7.12 (dd, 1H, J = 8.1, 7.5 Hz), 6.93 (dd, 1H, J = 8.1, 1.6 Hz), 6.80 ( dd, 1H, J = 7.4, 1.6 Hz), 5.57 (s, 2H), 3.81 (s, 3H).

References

[1] Patent: WO2004/63198, 2004, A1. Location in patent: Page 77
[2] Tetrahedron, 2010, vol. 66, # 29, p. 5402 - 5406
[3] Tetrahedron, 2000, vol. 56, # 2, p. 165 - 173
[4] Journal of Organic Chemistry, 1988, vol. 53, # 6, p. 1170 - 1176
[5] Patent: EP950657, 1999, A2