反应详情

温度

0 °C

To a solution of 2-(4-chloro-7-methylquinazolin-2-yl)phenol (0.478 g, 1.76 mmol) in CH2Cl2 was added triethylamine (0.98 mL, 0.712 g, 7.04 mmol), and the mixture was cooled to 0° C. To the reaction mixture was added tert-butyl ((R)-piperidin-3-yl)methylcarbamate oxalate (prepared analogously to 2-(7-Methyl-4-piperazin-1-yl-quinazolin-2-yl)-phenol, oxalate salt, see Example 130; 700 mg, 2.3 mmol). The reaction was allowed to warm to room temperature and was stirred overnight. The reaction was quenched with water, and the aqueous layer was extracted with CH2Cl2. The combined organic layers were dried over MgSO4, filtered, and concentrated. Purification via silica gel chromatography using 0-2% EtOAc in CH2Cl2 gave tert-butyl ((S)-1-(2-(2-hydroxyphenyl)-7-methylquinazolin-4-yl)piperidin-3-yl)methylcarbamate (700 mg, 88%). LC/MS: nm/z 449.5 (M+H)+ at 2.77 min (10%-99% CH3CN (0.035% TFA)/H2O (0.05% TFA)).

1. temperatureto warm to room temperature
2. customThe reaction was quenched with water
3. extractionthe aqueous layer was extracted with CH2Cl2
4. dry with materialThe combined organic layers were dried over MgSO4
5. filtrationfiltered
6. concentrationconcentrated
7. customPurification via silica gel chromatography