Sodium Hydroxide → HCID 131728342, compound

Participants

Reaction Steps

In a 250 mL round-bottom flask equipped with a magnetic stirrer is dissolved compound A1 (4.72 g, 6.97 mmol) in EtOH (100 mL). To this is then added aq. 1M NaOH (50 mL), and the resulting colorless sol. is heated to 80° C. for 14 h. The resulting pale pink sol. is allowed to cool to rt, and carefully acidified to a pH of 1.5. The volatiles are removed in vacuo and the resulting residue is partitioned between EtOAc (300 mL) and water (300 mL). The aq. phase is separated and back-extracted with EtOAc (3×300 mL). The combined org. extracts are then washed with brine (500 mL), decolorized with activated charcoal and dried over MgSO4. Filtration through a bed of Celite and concentration of the colorless filtrate in vacuo affords a white froth. Separation of (rac.)-(1R*,5S*)-7-{4-[3-(2-chloro-3,6-difluoro-phenoxy)-propyl]-phenyl}-3,9-diaza-bicyclo[3.3.1]non-6-ene-3,6,9-tricarboxylic acid 3,9-di-tert-butyl ester [1.01 g, 22%; Rf=0.55 (1:1 Hex:EtOAc+1% AcOH)] and the title compound (2.77 g, 61%) can be achieved by way of FC (SiO2, 2:1 hexane:EtOAc+1% AcOH). Residual AcOH can be removed quantitatively by first azeotroping with heptane and then toluene. Rf=0.50 (1:1 Hex:EtOAc+1% AcOH); ES−=646.8.

Provenance & Evidence