Synthesis
Example 14: Synthesis of methyl 5-((1R,2S)-2-((S)-4-(4-chlorophenyl)-4-hydroxy-3,3-dimethylpiperidine-1-carbonyl)cyclohexylcarbamoyl)biphenyl-3-carboxylate
Step 1: Preparation of 3-amino-5-(methoxycarbonyl)benzoic acid
Under argon protection, 20% Pd(OH)2 (0.50 g) was carefully wetted with methanol (5 mL), followed by addition of a methanol (20 mL) solution of 3-(methoxycarbonyl)-5-nitrobenzoic acid (5.00 g, 22.2 mmol). The mixture was placed in a Parr shaker and hydrogenated under 50 psi hydrogen pressure for 5 hours. Upon completion of the reaction, the reaction mixture was carefully filtered through glass fiber filter paper under argon protection. The filtrate was concentrated to give the off-white solid product 3-amino-5-(methoxycarbonyl)benzoic acid (4.0 g, 20.5 mmol, 92% yield). Mass spectrometry analysis resulted in (M-H)+ = 194.
References
[1] Patent: WO2009/15166, 2009, A1. Location in patent: Page/Page column 87
[2] Chemical Communications, 2012, vol. 48, # 40, p. 4809 - 4811
[3] Bioorganic and Medicinal Chemistry Letters, 2009, vol. 19, # 10, p. 2654 - 2660
[4] Patent: US2007/32470, 2007, A1. Location in patent: Page/Page column 8-9
[5] Patent: US2006/223759, 2006, A1. Location in patent: Page/Page column 193
