反应详情

To a solution of 94.6 mg (0.3 mmol) of (3R)-3-[(tert-butoxycarbonyl)amino]-4-(2,5-difluorophenyl)butanoic acid (Intermediate 1) in 1.5 mL of anhydrous dichloromethane, stirred in an ice bath under protection from moisture, was added 0.0106 mL (10.8 mmol) of anhydrous 98% hydrazine. Then 91.8 mg of 1-hydroxybenzotriazole hydrate was added, followed by 63.4 mg (0.33 mmol) of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDC) and finally 0.0574 mL (42.6 mg, 0.33 mmol) of N,N-diisopropylethylamine. After 15 minutes, an additional 0.0574 mL (42.6 mg, 0.33 mmol) of N,N-diisopropylethylamine was added. After 2 h, the mixture was removed from the ice bath and allowed to warm to room temperature, and precipitation gradually increased. After 22 h, the precipitated solid was collected on a filter, washed with small volumes of dichloromethane, and dried to give the title compound as a white solid, mp 168-169° C. LC-MS 230 (M+1-Boc).

1. waitAfter 2 h
2. customthe mixture was removed from the ice bath
3. customprecipitation
4. temperaturegradually increased
5. waitAfter 22 h
6. customthe precipitated solid was collected on a filter
7. washwashed with small volumes of dichloromethane
8. customdried