Acetic Acid → HCID 19809483, compound

Participants

Reaction Conditions

Reaction Steps

A solution of (±)5-(2-amino-1,3-oxazol-5-yl)-1-azabicyclo[3.2.1]octane (E3) (0.2g, 1 mmole) in dry tetrahydrofuran (10 ml) was treated with di-t-butyl dicarbonate (0.24g, 1.1 mmole) then stirred under nitrogen for 1h. The reaction mixture was concentrated in vacuo, treated with saturated aqueous potassium carbonate solution (10 ml) then extracted into chloroform (3×10 ml). The combined organic extracts were dried over sodium sulphate then concentrated in vacuo to a gum which was dissolved in dry diethyl ether (5 ml) then treated with benzyl bromide (0.18g, 1 mmole). After stirring for 17h under nitrogen, the supernatant was removed and the residual white solid washed with ether and dried in vacuo. A solution of this material in dry N,N-dimethylformamide was treated with sodium hydride (24 mg, 1.0 mmole) and heated at 40° C. until the evolution of hydrogen ceased. Methyl p-toluenesulphonate (146 mg, 0.78 mmole) was added and the mixture was heated to 50° C. After 8h additional quantities of sodium hydride (12 mg) and methyl p-toluenesulphonate (73 mg) were added and the reaction was heated at 50° C. for 19h. Concentration in vacuo followed by trituration with ether afforded a yellow solid which was dissolved in ethanol, treated with 10% Palladium on charcoal (0.04g) and acetic acid (43 mg, 0.71 mmole) then stirred under hydrogen for 1h. The reaction mixture was filtered through celite, then concentrated in vacuo to a gum which was treated with saturated aqueous potassium carbonate (20 ml) and extracted into chloroform (3×25 ml). The combined organic extracts were dried over sodium sulphate then concentrated in vacuo. Chromatography on neutral alumina in a gradient of 0-2% methanol in chloroform afforded the faster running component as a gum which was dissolved in dry dichloromethane (5 ml) and treated with anisole (70 mg, 0.65 mmole) followed by trifluoroacetic acid (0.3, 2.6 mmole) at 0° C. After stirring at room temperature for 1.75 h the solvent was removed in vacuo, the residue was dissolved in water and washed with pentane (5×25 ml). The aqueous layer was basified with potassium carbonate and extracted into chloroform (3×20 ml). The organic extracts were dried over sodium sulphate then concentrated in vacuo. The residue was chromatographed on basic alumina in a gradient of 0-2% methanol in chloroform to afford the title compound (E15) as a clear gum (8 mg).

Provenance & Evidence