反应详情

Dissolve (E)-3-dipropylcarbamoyl-2-methylacrylic acid (0.029 g, 0.134 mmol) in dichloromethane (1.3 mL). Add 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDCl) (0.028 g, 0.148 mmol) then 1-hydroxybenzotriazole (HOBT) (0.023 g, 0.148 mmol). Stir at room temperature for 30 minutes. To this stirring solution add (2R,5R)-5-[(1S,2S)-2-amino-3-(3,5-difluorophenyl)-1-hydroxypropyl]-2-cyclohexyloxymethylmorpholine-4-carboxylic acid tert-butyl ester (0.065 g, 0.134 mmol) in dichloromethane (1.5 mL). Stir for 2.5 hours, quench with 10% aqueous potassium carbonate (20 mL), and dilute with dichloromethane (75 mL). Extract the organic layer, wash with 5% aqueous citric acid (25 mL), saturated aqueous sodium chloride (30 mL), dry (magnesium sulfate) and purify (silica gel chromatography, eluting with 30:70 to 70:30 ethyl acetate:hexanes) to give the title compound as a white foam (0.041 g, 45.2%).

1. stirringStir for 2.5 hours
2. customquench with 10% aqueous potassium carbonate (20 mL)
3. additiondilute with dichloromethane (75 mL)
4. extractionExtract the organic layer
5. washwash with 5% aqueous citric acid (25 mL), saturated aqueous sodium chloride (30 mL)
6. dry with materialdry (magnesium sulfate)
7. custompurify
8. wash(silica gel chromatography, eluting with 30:70 to 70:30 ethyl acetate:hexanes)