1,3-Dibromopropane → HCID 68680811, compound

Participants

Reaction Conditions

Reaction Steps

To a stirred solution of 1-[3-(tert-butyldimethylsilanyloxy)propyl]imidazolidin-2-one (38 g, 147 mmol; prepared as described in Preparation 5) in DMF (500 mL) was added NaH (6.4 g, 60% in mineral oil, 160 mmol). The reaction was then heated to 50° C. and was allowed to stir until bubbling of H2 ceased (˜1 hours). The reaction was then cooled to room temperature. To the reaction mixture was dropwise added 1,3-dibromopropane (14.0 mL, 147 mmol). The reaction was allowed to stir at room temperature for 16 hours. Next, DIPEA (52 mL, 294 mmol) and biphenyl-2-ylcarbamic acid piperidin-4-yl ester (47 g, 160 mmol; prepared as described in Preparation 3) was added to the reaction and this was heated to 50° C. for 18 hours. After 18 hours, the reaction was cooled to room temperature and then condensed under reduced pressure. The crude reaction mixture was dissolved in 1:1 mixture of 1N HCl:ACN (250 mL) and heated to 50° C. for 5 hours. The reaction was then condensed under reduced pressure, dissolved in DCM (500 mL), washed with 1N HCl (500 mL), water (500 mL), NaCl (sat.) (500 mL), dried over MgSO4 and then filtered. The solvent was removed under reduced pressure. The crude material was purified via silica gel chromatography (10% MeOH/DCM w/1% NH3 (aq)) to afford the title compound in 9.8% yield (8.6 g, 14.4 mmol).

Provenance & Evidence