反应详情

温度

0 °C

3-(S)-Hydroxytetrahydrofuran (4.8 mL, 60.7 mmols, 5 eq) was dissolved in 60 mL of toluene. The solution was cooled to 0° C. and Et3N (5.1 mL, 36.4 mmols, 3 eq) was added. Trichloromethyl chloroformate (3.65 mL, 30.33 mmols, 2.5 eq) was added slowly. The solution was stirred at 0° C. for 45 min. 3-Amino-5-nitrobenzotrifluoride (2.5 g, 12.13 mmols, 1 eq) was added dropwise in 20 mL of toluene. The reaction was stirred at 0° C. for 1 h. An additional 5 eq of 3-(S)-hydroxytetrahydrofuran was converted to the chloroformate as described above, and added to the reaction mixture. After an additional h at 0° C., the reaction was heated to 60° C. for 1 h. The reaction was cooled to RT and concentrated. The residue was dissolved in EtOAc, washed twice with saturated NH4Cl and once with brine. After being dried over Na2SO4 the solution was filtered and the solvent removed in vacuo. The crude product was purified using a Biotage chromatography system eluting with a gradient of 5% to 35% EtOAc:hexane to yield the desired compound.

1. stirringThe reaction was stirred at 0° C. for 1 h
2. additionadded to the reaction mixture
3. temperatureAfter an additional h at 0° C., the reaction was heated to 60° C. for 1 h
4. temperatureThe reaction was cooled to RT
5. concentrationconcentrated
6. dissolutionThe residue was dissolved in EtOAc
7. washwashed twice with saturated NH4Cl and once with brine
8. dry with materialAfter being dried over Na2SO4 the solution
9. filtrationwas filtered
10. customthe solvent removed in vacuo
11. customThe crude product was purified
12. washeluting with a gradient of 5% to 35% EtOAc