反应详情

A stirred solution of Cbz-N(Me)Ala-OH (7.85 g, 7.70 mmol), HATU (2.95 g, 7.70 mmol), and DIPEA (1.60 mL, 9.10 mmol) in NMP (20 mL) was cooled to 0° C. and amine 47 (7.02 mmol) in NMP (20 mL) was added. The solution was allowed to warm to ambient temperature. After 13 h, the reaction mixture was cooled to 0° C. and 1N NaOH (10 mL) was added. The reaction mixture was diluted with water and extracted with Et2O. The combined organic extracts were washed successively with water, 1N HCl, 10% H3PO4, water, NaHCO3, water, and brine. The organic layer was dried over anhydrous Na2SO4, filtered, and concentrated to afford 4.5 g (96%, 2 steps) of 48 as a white foam which was used without further purification. Mass spectrum, m/z [691.2] (M+Na)+.

1. temperaturethe reaction mixture was cooled to 0° C.
2. extractionextracted with Et2O
3. washThe combined organic extracts were washed successively with water, 1N HCl, 10% H3PO4, water, NaHCO3, water, and brine
4. dry with materialThe organic layer was dried over anhydrous Na2SO4
5. filtrationfiltered
6. concentrationconcentrated