反应 #542155
ord-f60a9453c3d84686abd40ee7905789bb
反应方程式
反应条件
后处理
- 1其他The excessive solvent was removed on ratovapor
- 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 (1.08 g, 6.45 mmol) in dichloromethane (50 ml) in an ice-bath was added oxalyl chloride (6.50 ml, 64.4 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 250 ml round-bottom flask was charged with {(R)-2-hydroxy-1-[4-((S)-2-methyl-butoxy)-phenyl]-ethyl}-amide HCl (6.47 mmol), dichloromethane (60 ml) and triethylamine (4.30 ml, 32.35 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 (3×30 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 (1.42 g, 58% yield): 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 7.25 (d, J=8.6 Hz, 2H), 7.09 (m, 1H), 6.91 (m, 3H), 6.82 (d, J=3.5 Hz, 1H), 6.23 (d, J=6.1 Hz, 1H), 5.06 (td, J=6.3, 4.3 Hz, 1H), 3.91 (m, 2H), 3.78 (m, 2H), 2.75 (m, 2H), 1.88 (m, 1H), 1.70 (m, 2H), 1.58 (m, 1H), 1.29 (m, 2H), 1.03 (d, J=6.8 Hz, 3H), 0.96 (t, J=7.5 Hz, 3H); LCMS (ESI) m/e 374.2 [(M+H)+, calcd for C21H28NO3S 374.5].