Synthesis
To a mixed toluene/methanol (30 ml, V/V=2:1) solution of cholic acid (2.0 g, 4.9 mmol) was added trimethylsilyl diazomethane (3.67 ml, 7.34 mmol), and the reaction was stirred for 2 h at 20 °C. The reaction was monitored by thin layer chromatography (TLC, spreader ratio of methanol/dichloromethane=1:10). The progress of the reaction was monitored by thin layer chromatography (TLC, spreading agent ratio methanol/dichloromethane=1:10) to confirm complete consumption of cholic acid and generation of new spots. Upon completion of the reaction, the reaction mixture was concentrated to afford (R)-methyl 4-((3R,5S,7R,8R,9S,10S,12S,13R,14S,17R)-3,7,12-trihydroxy-10,13-dimethyl-hexadecahydro-1H-cyclopenta[a]phenanthracen-17-yl)pentanoate (2.08 g, 100% yield) as a white foamy solid. Its hydrogen NMR spectrum (400MHz, CDCl3) data were as follows: δ 3.98(m, 1H, C12-H), 3.85(m, 1H, C7-H), 3.45(m, 1H, C3-H), 3.66(s, 3H, OCH3), 0.98(d, 3H, 21-Me), 0.89(s, 3H, 19-Me), 0.69 (s, 3H, 18-Me).
References
[1] Drug Metabolism and Disposition, 2017, vol. 45, # 7, p. 721 - 733
[2] Patent: WO2009/146218, 2009, A2. Location in patent: Page/Page column 141
[3] Tetrahedron Letters, 2010, vol. 51, # 1, p. 93 - 95
[4] Steroids, 2010, vol. 75, # 10, p. 701 - 709
[5] Tetrahedron Letters, 2011, vol. 52, # 52, p. 7128 - 7131
