反应详情

温度

85 °C

Prepared using General Procedure 2. To a solution of 4-phenyl-5-(trifluoromethyl)thiophene-2-carboxylic acid (0.109 g, 0.4 mmol) in DMF (3.0 mL) was added HOBt (0.088 g, 0.57 mmol) and EDC (0.109 g, 0.57 mmol) at room temperature. The reaction mixture was stirred for 0.5 h until the complete formation of the HOBt-acid complex. (R)-tert-butyl 2-(tert-butyldimethylsilyloxy)ethyl(4-(N-hydroxycarbamimidoyl)-2,3-dihydro-1H-inden-1-yl)carbamate INT-61 (0.200 g, 0.44 mmol) was added and the mixture was stirred at room temperature for 0.5 h until the formation of the intermediate (R)-tert-butyl 2-(tert-butyldimethylsilyloxy)ethyl(4-(N-(4-phenyl-5-(trifluoromethyl)thiophene-2-carbonyloxy) carbamimidoyl)-2,3-dihydro-1H-inden-1-yl) carbamate was observed. The reaction mixture was heated at 85° C. for 4 h. Upon cooling, the mixture was extracted with DCM and brine. The combined organic layers were dried over MgSO4, filtered, and concentrated under reduced pressure to produce a brown oil. The crude product was purified by silica gel flash chromatography (MeOH/DCM) to yield 0.108 g (40%) of (R)-tert-butyl 2-(tert-butyldimethylsilyloxy)ethyl(4-(5-(4-phenyl-5-(trifluoromethyl)thiophen-2-yl)-1,2,4-oxa-diazol-3-yl)-2,3-dihydro-1H-inden-1-yl)carbamate INT-63 as a light yellow oil. LCMS-ESI (m/z) calculated for C35H42F3N3O4SSi: 685.9; found 411.0 [M+H−tert-butyl 2-(tert-butyldimethylsilyloxy)ethylcarbamate]+, tR=4.01 min.

1. customPrepared
2. addition(0.200 g, 0.44 mmol) was added
3. temperatureUpon cooling
4. extractionthe mixture was extracted with DCM and brine
5. dry with materialThe combined organic layers were dried over MgSO4
6. filtrationfiltered
7. concentrationconcentrated under reduced pressure
8. customto produce a brown oil
9. customThe crude product was purified by silica gel flash chromatography (MeOH/DCM)