反応 #48661

反応方程式

1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride

(E)-3-dipropylcarbamoyl-2-methylacrylic acid

(2R,5R)-5-[(1S,2S)-2-amino-3-(3,5-difluorophenyl)-1-hydroxypropyl]-2-cyclohexyloxymethylmorpholine-4-carboxylic acid tert-butyl ester

1-hydroxybenzotriazole

→

title compound

収率 45.2%

(2R,5R)-2-Cyclohexyloxymethyl-5-[(1S,2S)-3-(3,5-difluorophenyl)-2-((E)-3-dipropylcarbamoyl-2-methylacryloylamino)-1-hydroxypropyl]-morpholine-4-carboxylic acid tert-butyl ester

収率 45.2%

溶媒

dichloromethane

dichloromethane

反応条件

後処理

1. 1
   workup.STIRRINGStir for 2.5 hours
2. 2
   その他quench with 10% aqueous potassium carbonate (20 mL)
3. 3
   workup.ADDITIONdilute with dichloromethane (75 mL)
4. 4
   抽出Extract the organic layer
5. 5
   洗浄wash with 5% aqueous citric acid (25 mL), saturated aqueous sodium chloride (30 mL)
6. 6
   乾燥dry (magnesium sulfate)
7. 7
   その他purify
8. 8
   洗浄(silica gel chromatography, eluting with 30:70 to 70:30 ethyl acetate:hexanes)

実験手順

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%).

出典