反应详情

温度

0 °C

In a 25 mL 3N round-bottomed flask equipped with nitrogen inlet, (Z)-3-(3-(3,5-bis(trifluoromethyl)phenyl)-1H-1,2,4-triazol-1-yl)acrylic acid (4) (0.250 g, 1.0 eq.) was charged along with dichloromethane (5.0 mL, 20 V). The reaction mixture was cooled to 0° C. and then added HOBT (0.119 g, 1.1 eq.) followed by EDC HCl (0.149 g, 1.1 eq.) and 3-methyl azetidin-3-ol HCl (0.096 g g, 1.1 eq.). DIPEA (0.101 g, 1.1 eq) was added to this reaction mixture dropwise at the same temperature. The clear reaction mixture was stirred at 0° C. for 1.5 h. The progress of the reaction was followed by TLC analysis on silica gel with 10% methanol in dichloromethane as mobile phase and visualization with UV. Reaction mixture was quenched in 20 mL ice-water slurry. Organic layer was separated and aqueous layer was extracted with dichloromethane (2×10 mL) to ensure complete extraction. The organic layer was washed with brine solution and dried over anhydrous Na2SO4 and concentrated by rotary evaporation under reduced pressure (35° C., 20 mm Hg) to afford 0.280 g of crude compound. (cis: 61.9%, trans: 16.46%)

1. customIn a 25 mL 3N round-bottomed flask equipped with nitrogen inlet
2. customReaction mixture
3. customwas quenched in 20 mL ice-water slurry
4. customOrganic layer was separated
5. extractionaqueous layer was extracted with dichloromethane (2×10 mL)
6. extractionextraction
7. washThe organic layer was washed with brine solution
8. dry with materialdried over anhydrous Na2SO4
9. concentrationconcentrated by rotary evaporation under reduced pressure (35° C., 20 mm Hg)