Hydrochloric Acid → HCID 44828663, compound

Participants

Reaction Steps

Benzyl ((S)-1-(tert-butoxycarbonyl)piperidin-3-yl)methylcarbamate (1.2 g, 3.54 mmol) was treated with 4.0 M HCl solution in dioxane (4.3 mL, 17.2 mmol). Formation of a white precipitate was observed. The reaction was complete after three hours. The solvent and excess HCl were removed under reduced pressure to obtain benzyl ((S)-piperidin-3-yl)methylcarbamate hydrochloride as a white solid. This solid was suspended in DMF/CH2Cl2 (3 mL/3 mL), followed by the addition of 2-(4-chloro-7-methylquinazolin-2-yl)phenol (958 mg, 3.54 mmol) and then triethylamine (1.8 mL, 1.3 g, 12.85 mmol). The mixture was stirred at room temperature under an N2 atmosphere for 16 h. The reaction was then partitioned between H2O and CH2Cl2, separated, and the aqueous layer was extracted twice with CH2Cl2. The combined organic layers were dried over Na2SO4, filtered, and concentrated under reduced pressure. Purification via silica gel chromatography using 0-5% MeOH in CH2Cl2 gave benzyl((R)-1-(2-(2-hydroxyphenyl)-7-methylquinazolin-4-yl)piperidin-3-yl)methylcarbamate as a thick yellow oil (855 mg, 51%). LC/MS: m/z 483.5 (M+H)+ at 2.81 min (10%-99% CH3CN (0.035% TFA)/H2O (0.05% TFA)).

Provenance & Evidence