反应详情

Ethyl diazoacetate (0.478 g, 1.19 mmol) in dry CH2Cl2 (15 mL) was slowly added dropwise to a stirred suspension of 3α,7α-diacetoxy-5-norcholan-22,23-ene (1) (0.6 g, 1.39 mmol) in the presence of dirhodium (II) tetraacetate (9 mg, 0.02 mmol) in dry CH2Cl2 (15 mL) under nitrogen at room temperature. The reaction mixture was filtered and washed with H2O (20 mL), dried (Na2SO4), and evaporated under vacuum, thus affording a mixture of the four diastereoisomeric esters 2. The esters 2 were successively dissolved in EtOH (15 mL) and treated with a solution of 10 N NaOH (10 mL) at reflux for 4 h, cooled, poured onto cold H2O (50 mL), acidified with 2 N HCl, and extracted with EtOAc (3×15 mL). The organic phase was washed with brine (10 mL), dried (Na2SO4), and concentrated under vacuum. The residue was chromatographated on silica gel. Elution with CH2Cl2/MeOH 96/4 with AcOH 0.1% afforded 0.087 g (15% yield) of (22S,23S)-3α,7α-dihydroxy-22,23-methylene-5β-cholan-24-oic acid (Io5) and 0.065 g (11.5% yield) of (22R,23R)-3α,7α-dihydroxy-22,23-methylene-5β-cholan-24-oic acid (Iq5). Elution with CH2Cl2/MeOH 95.5/4.5 with 0.1% AcOH afforded 0.18 g (32% yield) of (22S,23R)-3α,7α-dihydroxy-22,23-methylene-5β-cholan-24-oic acid (Ip5) and 0.15 g (26.7% yield) of (22R,23S)-3α,7α-dihydroxy-22,23-methylene-5β-cholan-24-oic acid (Ir5) as white solids.

1. filtrationThe reaction mixture was filtered
2. washwashed with H2O (20 mL)
3. dry with materialdried (Na2SO4)
4. customevaporated under vacuum
5. customthus affording
6. temperatureat reflux for 4 h
7. temperaturecooled
8. extractionextracted with EtOAc (3×15 mL)
9. washThe organic phase was washed with brine (10 mL)
10. dry with materialdried (Na2SO4)
11. concentrationconcentrated under vacuum
12. washElution with CH2Cl2/MeOH 96/4 with AcOH 0.1%