Hydrochloric Acid → 7-{4-[3-(tert-Butyldimethylsilanyloxy)propyl]thiazol-2-yl}-3,9-diazabicyclo[3.3.1]non-6-ene-3,6,9-tricarboxylic acid 3,9-di-tert-butyl ester

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Reaction Conditions

Reaction Steps

A mixture of compound C2 (5.46 g, 10.2 mmol) in EtOH (120 mL) and aq. 1M NaOH (120 mL) was stirred at 80° C. for 90 min. 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 (120 mL). Imidazole (2.77 g, 40.6 mmol) and TBDMS-Cl (3.83 g, 25.4 mmol) were added. The mixture was stirred overnight. Aq. sat. NH4Cl (500 mL) 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 (75 mL), MeOH (25 mL) and H2O (25 mL), and K2CO3 (702 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 (500 mL). 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. Purification of the residue by FC (EtOAc/heptane 1:1→MeOH/EtOAc 1:9) yielded the title compound (2.90 g, 46%). LC-MS: tR=1.15 and 1.19 min, ES+: 624.47.

Provenance & Evidence