反应详情

温度

-15 °C

(2R,3S)-2-(3-chloro-4-cyanophenylamino)-3-hydroxybutanoic acid (3.33 g, 13.07 mmol), 4-(methylsulfonyl)benzohydrazide (3.08 g, 14.38 mmol) and anhydrous THF (200 mL) were placed in a 500 mL round bottomed flask and the mixture was cooled to −15° C. 1-Hydroxybenzotriazole hydrate (1.77 g, 13.07 mmol) was added to the mixture together with N-(3-Dimethylaminopropyl)-N′-ethylcarbodimide HCl (3.76 g, 19.61 mmol) at −15° C. followed by triethylamine (2.73 mL, 19.61 mmol). The reaction mixture was maintained at −15° C. and stirred for 1 h after which, stirring continued overnight while the mixture slowly warmed to room temperature. After 17 h, the mixture was filtered under vacuum and the residue washed with THF (50 mL). The THF solution was concentrated to ca. 20 mL, whereupon EtOAc (100 mL) was added followed by water (50 mL). The phases were partitioned and the organic phase washed with water (30 mL), brine (30 mL) dried (Na2SO4) and concentrated to furnish a light brown solid (5.82 g). This crude product was chromatographed [100% EtOAc as eluent] to afford a pale yellow solid (5 g). The crude product was used directly in the next step.

1. temperatureThe reaction mixture was maintained at −15° C.
2. stirringstirring
3. waitcontinued overnight while the mixture
4. temperatureslowly warmed to room temperature
5. waitAfter 17 h
6. filtrationthe mixture was filtered under vacuum
7. washthe residue washed with THF (50 mL)
8. concentrationThe THF solution was concentrated to ca. 20 mL, whereupon EtOAc (100 mL)
9. additionwas added
10. customThe phases were partitioned
11. washthe organic phase washed with water (30 mL), brine (30 mL)
12. dry with materialdried (Na2SO4)
13. concentrationconcentrated