Hydrochloric Acid → Ammonia

Participants

Reaction Steps

tert-butyl{2-[4-(2-{4-(benzyloxy)-3-[(1R)-3-(diisopropylamino)-1-phenylpropyl]phenyl}ethoxy)phenyl]ethyl}carbamate (Preparation 41, 830 mg, 1.25 mmol) was treated with hydrochloric acid (8 ml of a 4M solution in 1,4-dioxane) and stirred at room temperature overnight, and the solvent was removed in vacuo. The residue was dissolved in acteonitrile (8 ml) and {2-(benzyloxy)-5-[(1R)-2-bromo-1-{[tert-butyl(dimethyl)silyl]oxy}ethyl]phenyl}methanol (Sali patent, 560 mg, 1.24 mmol) and sodium hydrogen carbonate (368 mg, 4.34 mmol) added. Mixture heated to 85° C. and stirred overnight. Reaction was cooled to room temperature and ethyl acetate and water added, the aqueous layer was separated and washed with ethyl acetate and the combined organics dried (magnesium sulphate) and the solvent removed in vacuo. The residue was purified by column chromatography on silica gel eluting with dichloromethane:methanol:880 ammonia (92.517.511 by volume) to furnish the title compound as a gum, 280 mg.

Provenance & Evidence