反応 #48635

反応方程式

acetic anhydride

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

triethylamine

→

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

溶媒

tetrahydrofuran

反応条件

後処理

1. 1
   濃縮Concentrate
2. 2
   その他purify
3. 3
   洗浄(silica gel chromatography, eluting with 80:20 ethyl acetate:dichloromethane)
4. 4
   その他to separate the two title compounds 5-(R)-[2-(S)-acetylamino-3-(3,5-difluorophenyl)-1-(S)-hydroxypropyl]-2-(S)-(3-methylbutyl)-morpholine-4-carboxylic acid tert-butyl ester (0.141 g, 59%) and 5-(S)-[2-(R)-acetylamino-3-(3,5-difluorophenyl)-1-(R)-hydroxypropyl]-2-(S)-(3-methylbutyl)-morpholine-4-carboxylic acid tert-butyl ester (25.1 mg, 22%)

実験手順

Add acetic anhydride (25 μL, 0.264 mmol) to a solution of 5-(R)-[2-(S)-amino-3-(3,5-difluorophenyl)-1-(S)-hydroxypropyl]-2-(S)-(3-methylbutyl)-morpholine-4-carboxylic acid tert-butyl ester (107 mg, 0.240 mmol) and triethylamine (37 μL, 0.267 mmol) in tetrahydrofuran (5 mL) and stir at room temperature for 18 hours. Concentrate and purify (silica gel chromatography, eluting with 80:20 ethyl acetate:dichloromethane), to separate the two title compounds 5-(R)-[2-(S)-acetylamino-3-(3,5-difluorophenyl)-1-(S)-hydroxypropyl]-2-(S)-(3-methylbutyl)-morpholine-4-carboxylic acid tert-butyl ester (0.141 g, 59%) and 5-(S)-[2-(R)-acetylamino-3-(3,5-difluorophenyl)-1-(R)-hydroxypropyl]-2-(S)-(3-methylbutyl)-morpholine-4-carboxylic acid tert-butyl ester (25.1 mg, 22%).

出典