Hydrochloric Acid → 7-{3-[3-(tert-Butyldimethylsilanyloxy)propyl]isoxazol-5-yl}-3,9-diazabicyclo[3.3.1]non-6-ene-3,6,9-tricarboxylic acid 3-tert-butyl ester 9-(2,2,2-trichloro-1,1-dimethylethyl) ester

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Reaction Conditions

Reaction Steps

A mixture of compound C3 (1.03 g, 1.40 mmol) in EtOH (10 mL) and aq. 1M NaOH (10 mL) was stirred at 80° C. for 5 h. The mixture was allowed to cool to rt, and was then diluted with EtOAc. This mixture was acidified with aq. 1M HCl until a pH between 3 and 4 was obtained. The layers were separated, then the aq. phase was extracted with EtOAc (2×). The combined org. extracts were dried over MgSO4, filtered, and the solvents were removed under reduced pressure. The crude product was dissolved in DMF (20 mL). Imidazole (381 mg, 5.6 mmol) and TBDMS-Cl (527 mg, 3.5 mmol) were added. The mixture was stirred overnight. Aq. sat. NH4Cl was added and the resulting suspension was extracted with heptane (3×). The combined org. extracts were dried over MgSO4, filtered, and concentrated to yield a yellow oil. This crude product was dissolved in THF (15 mL), MeOH (5 mL) and H2O (5 mL), and K2CO3 (97 mg) was added. The mixture was stirred at rt for 2.5 h and was concentrated to half under reduced pressure. The residue was then diluted with Et2O to produce a clear yellow sol. This yellow sol. was washed with aq. sat. NH4Cl. The aq. phase was extracted with Et2O (2×), and the combined org. extracts were dried over MgSO4, filtered, and the solvents were removed under reduced pressure. The crude title compound (950 mg, 95%) was used without further purification.

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