反应详情

(S)-3-(R)-2-Ethyl-1-hydroxybutyl)pyrrolidine-1-carboxylic acid t-butyl ester (28 mg, 0.1 mmol) was dissolved in DMF (380 μL, 4.9 mmol). 60% Sodium hydride in oil (0.4:0.6, sodium hydride:mineral oil, 18.6 mg, 310 μmmol) was slowly added, and the resulting mixture was stirred at room temperature for 15 minutes. 1,2-Dichloro-3-fluorobenzene (23.8 μL, 206 μmmol) was added and the mixture was stirred at 70° C. for 3 hours. The mixture was concentrated, treated with 1.25M HCl in EtOH (578 μL, 722 μmmol), then stirred overnight at room temperature. The product was concentrated under vacuum, redissolved in 1:1AcOH:H2O, filtered, and purified by preparative HPLC to yield the title compound as a mono-TFA salt (5.3 mg, 97% purity). MS m/z: [M+H]+ calcd for C16H23Cl2NO, 316.12; found 316.3.

1. stirringthe mixture was stirred at 70° C. for 3 hours
2. concentrationThe mixture was concentrated
3. additiontreated with 1.25M HCl in EtOH (578 μL, 722 μmmol)
4. stirringstirred overnight at room temperature
5. concentrationThe product was concentrated under vacuum
6. dissolutionredissolved in 1:1AcOH
7. filtrationH2O, filtered
8. custompurified by preparative HPLC