Methyl 4-broMobicyclo[2.2.2]octane-1-carboxylate

Synthesis

4-(Methoxycarbonyl)bicyclo[2.2.2]octane-1-carboxylic acid (XVIII-1, 10 g, 47.2 mmol) was used as a raw material, which was dissolved in dibromomethane (CH2Br2, 100 mL) at room temperature and mercuric oxide (HgO, 17.5 g, 80.3 mmol) was added with stirring. The reaction mixture was heated to 80 °C and bromine (Br2, 3.6 mL, 47.2 mmol) was added slowly and dropwise over 40 min. After the dropwise addition was completed, the reaction continued to be stirred at 80 °C for 3 hours. After completion of the reaction, the mixture was cooled to room temperature and filtered to remove insoluble material. The filtrate was dried with anhydrous magnesium sulfate (MgSO4), filtered and concentrated under reduced pressure. The resulting residue was methyl 4-bromobicyclo[2.2.2]octane-1-carboxylate (XVIII-2, 11 g, 94.8% yield), which was used directly in the next step of the reaction without further purification.

References

[1] Bioorganic and Medicinal Chemistry Letters, 2014, vol. 24, # 24, p. 5731 - 5737
[2] Patent: US2014/200215, 2014, A1. Location in patent: Paragraph 1092
[3] Journal of Medicinal Chemistry, 2009, vol. 52, # 6, p. 1558 - 1568
[4] Patent: WO2015/5901, 2015, A1. Location in patent: Page/Page column 468
[5] Patent: WO2006/128184, 2006, A2. Location in patent: Page/Page column 171