反应 #542168

ord-f7ed910057ce477e8aa722eb054e6793

反应条件

温度
0°CELSIUS
详细条件
See reaction.notes.procedure_details.

后处理

  1. 1
    其他The excessive solvent was removed on ratovapor
  2. 2
    其他dried under high vacuum for 2 hrs

实验过程

To a solution of (1S,2S)-2-thiophen-2-yl-cyclopropanecarboxylic acid (228.2 mg, 1.36 mmol) in dichloromethane (10 ml) in an ice-bath was added oxalyl chloride (0.58 ml, 6.6 mmol), then DMF (0.1 ml) under nitrogen. The reaction mixture was stirred for 30 minutes at 0° C. The excessive solvent was removed on ratovapor and dried under high vacuum for 2 hrs to give (1S,2S)-2-thiophen-2-yl-cyclopropanecarboxylic chloride. In a separated flask was charged with above aminoalcohol (1.36 mmol), dichloromethane (5 ml) and DIEA (448 uL, 2.72 mmol) in an ice cold bath under nitrogen. The (1S,2S)-2-thiophen-2-yl-cyclopropanecarboxylic chloride, made freshly in dichloromethane (10 ml) was added into the reaction mixture dropwise. The final reaction mixture was stirred for 1.5 hrs at room temperature. The finished reaction was quenched with water. The organic phase was washed with brine (3×10 ml), dried over MgSO4, filtrated, concentrated in vacuum and purified via column chromatography on silica gel with a gradient of 0%-100% of ethyl acetate in hexane to give a white solid (393.4 mg, 59% yield).

来源

DOI: 10.6084/m9.figshare.5104873.v1专利: US08497271B2uspto-grants-2013_07