Uses
Methyl 2-(2-bromophenyl)acetate is a reagent in the synthesis of 2,3,3a,12b-Tetradehydro Asenapine (T291630). 2,3,3a,12b-Tetradehydro Asenapine is a degredation product of Asenapine (A788000), a combined serotonin (5HT2) and dopamine (D2) receptor antagonist; structurally related to Mianserin. Antipsychotic.
Synthesis
General method: o-Bromophenylacetic acid (5.0 g, 18.18 mmol) was dissolved in methanol (50 mL) containing a catalytic amount of concentrated sulfuric acid and the reaction was refluxed for 30 minutes. Upon completion of the reaction, the mixture was cooled to room temperature and concentrated under reduced pressure to remove the solvent. Water (30 mL) was added to the residue, which was subsequently extracted with dichloromethane (3 x 20 mL). The organic layers were combined, dried over anhydrous sodium sulfate and the solvent was evaporated under reduced pressure to give the corresponding methyl 2-(2-bromophenyl)acetate products. The products were: methyl 2-(2-bromo-4,5-dimethoxyphenyl)acetate (S5a, 5.19 g, 99%, brown oil); methyl 2-(2-bromo-5-methoxyphenyl)acetate (S5b, 2.09 g, 99%, brown oil); methyl 2-(2-bromo-4-methoxyphenyl)acetate (S5c, 2.09 g, 99%, brown oil ); methyl 2-(2-bromophenyl)acetate (S5d, 5.27g, 99%, clear oil).
References
[1] Journal of the American Chemical Society, 2003, vol. 125, # 11, p. 3268 - 3272
[2] Chemistry - An Asian Journal, 2011, vol. 6, # 8, p. 2040 - 2047
[3] Tetrahedron, 2013, vol. 69, # 42, p. 8914 - 8920
[4] Chemistry - A European Journal, 2016, vol. 22, # 34, p. 12166 - 12175
[5] Tetrahedron Letters, 2003, vol. 44, # 2, p. 331 - 334
