Acetic Acid → HCID 130473111, compound

Participants

Reaction Steps

o a solution of O2-tert-butyl O1-[(3R)-quinuclidin-3-yl] 3,4-dihydro-1H-isoquinoline-1,2-dicarboxylate (440 mg, 1.14 mmol) in ethyl acetate (1.42 mL) was added 4N HCl/dioxane (1.42 mL, 5.70 mmol) and the resultant solution was stirred at room temperature for 18 h. The solvent was removed in vacuo to give a white solid. The crude material (200 mg, 0.56 mmol) was dissolved in acetonitrile (5 mL) and [(1S)-2-(3,5-dichloro-1-oxido-pyridin-1-ium-4-yl)-1-(3,4-dimethoxyphenyl)ethyl]5-formylthiophene-2-carboxylate (270 mg, 0.56 mmol) was added followed by acetic acid (67 μL, 1.12 mmol). The resultant solution was stirred at room temperature for 18 h. The solvent was removed in vacuo and the residue azeotroped with toluene. The residue was rediluted with acetonitrile (5 mL) and sodium triacetoxyborohydride (237 mg, 1.12 mmol) was added and the resultant solution was stirred at room temperature for 18 h. The solvent was removed in vacuo and the residue was taken up in water (20 mL) and ethyl acetate (20 mL). The layers were separated and the aqueous phase was extracted with ethyl acetate (2×20 mL). The combined organic phases were extracted with 0.2 N aqueous hydrochloric acid (40 mL) and water (40 mL). The aqueous extracts were combined and sodium chloride (6 g) was added. The mixture was extracted with chloroform (3×30 mL) and the combined organic extracts were passed through a hydrophobic fit and the solvent was removed in vacuo. Purification of the crude material by preparative HPLC afforded the title compound (77 mg, 18%) as a pale yellow solid.

Provenance & Evidence