CC1(C)OC(=S)NC2C=CC(C3N(C)C(C#N)=CC=3)=CC1=2.[H-].[Na+].[C:24](=[O:26])=[O:25].CC([O:30][C@@H:31]1[C@@H:36]([O:37]C(C)=O)[C@@H](Br)[O:34][C@H:33]([C:42](OC)=[O:43])[C@H:32]1[O:46]C(C)=O)=O>CN(C)C=O>[O:37]=[CH:36][C@@H:31]([C@H:32]([C@@H:33]([C@@H:42]([C:24]([OH:26])=[O:25])[OH:43])[OH:34])[OH:46])[OH:30]A solution of tanaproget (0.292 g, 1.0 mmol) in anhydrous dimethyl formamide (DMF) (10 mL) was added dropwise under a nitrogen atmosphere to a solution of sodium hydride (NaH) (0.052 g, 2.2 mmol) in DMF (50 mL) that was cooled to approximately −70° C. (dry ice). After stirring for 10 min, a solution of acetobromo-α-D-Glucuronic acid methyl ester (0.396 g, 1 mmol) in DMF (10 mL) was added dropwise. The reaction solution was then warmed to room temperature, and stirred for a total of 24 hours. After 24 hours, the reaction solution was partitioned between water (100 mL) and ethyl acetate (100 mL). The aqueous layer was extracted again with ethyl acetate (100 mL). The combined organic layers were washed with saturated sodium chloride (NaCl) solution (100 mL), dried (magnesium sulfate, MgSO4), and the solvent removed in vacuo. Aliquots of the crude material were chromatographed under low-pressure reversed-phase C18 (RediSep/ISCO, 125×25 mm ID, 40 μm particle size) conditions with a gradient of 50-95% acetonitrile/water. Fractions eluting with 75-80% acetonitrile/water contained the S-protected (D)-Glucuronic acid derivative (2) of tanaproget. A total of approximately 200 mg of (2) was obtained at 95% purity based on NMR spectroscopic analysis (32% isolated yield). All chemicals were purchased from Aldrich (Milwaukee, Wis.) and used without further purification or drying.
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