反应详情

To a cooled (0-5° C.) solution of (3R)-(+)-3-Boc-aminopyrrolidine (12.0 g, 65 mmol) and triethylamine (19 mL, 129 mmol) in DMF (100 mL) was added a solution of 2-(4-chloro-7-methylquinazolin-2-yl)phenol (17.4 g, 64 mmol) in CH2Cl2 (500 mL) and DMF (100 mL). After stirring the mixture for 5 hours at room temperature, water (900 mL) was added. The aqueous layer was extracted with dichloromethane (3×300 mL), and the combined organic layers were washed with saturated aqueous NaCl solution (300 mL), dried over sodium sulfate, filtered, and evaporated to dryness under reduced pressure. The yellow residue (21 g) was treated with 100 mL methanol at room temperature. The solid was collected by filtration and was washed with methanol to yield tert-butyl (R)-1-(2-(2-hydroxyphenyl)-7-methylquinazolin-4-yl)pyrrolidin-3-ylcarbamate (15.1 g, 55%) as a yellow solid.

1. extractionThe aqueous layer was extracted with dichloromethane (3×300 mL)
2. washthe combined organic layers were washed with saturated aqueous NaCl solution (300 mL)
3. dry with materialdried over sodium sulfate
4. filtrationfiltered
5. customevaporated to dryness under reduced pressure
6. additionThe yellow residue (21 g) was treated with 100 mL methanol at room temperature
7. filtrationThe solid was collected by filtration
8. washwas washed with methanol