Dimethylformamide → (S)-3-[(R)-1-(2,3-Dichlorophenoxy)-2-ethylbutyl]pyrrolidine

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Reaction Steps

(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.

Provenance & Evidence