反应详情

To a stirred solution of 2-(4-((R)-3-(aminomethyl)piperidin-1-yl)-7-methylquinazolin-2-yl)phenol (150 mg, 0.43 mmol) under an N2 atmosphere at 0° C. was added triethylamine (87 mg, 0.86 mmol) followed by the dropwise addition of (R)-tetrahydrofuran-3-yl chloroformate (65 mg, 0.43 mmol). The reaction was allowed to warm to room temperature and was stirred for 2 h. The mixture was partitioned between H2O and CH2Cl2 and separated, and the aqueous layer was extracted twice with CH2Cl2. The organic layers were combined, dried over Na2SO4, filtered, and concentrated. Purification via silica gel chromatography using 4:1 CH2Cl2:EtOAc afforded (R)-tetrahydrofuran-3-yl ((R)-1-(2-(2-hydroxyphenyl)-7-methylquinazolin-4-yl)piperidin-3-yl)methylcarbamate. LC/MS: m/z 463.5 (M+H)+ at 2.34 min (10%-99%.CH3CN (0.035% TFA)/H2O (0.05% TFA)).

1. customThe mixture was partitioned between H2O and CH2Cl2
2. customseparated
3. extractionthe aqueous layer was extracted twice with CH2Cl2
4. dry with materialdried over Na2SO4
5. filtrationfiltered
6. concentrationconcentrated
7. customPurification via silica gel chromatography