反应详情

温度

0 °C

(3S)-tert-butyl 4-(2-(3-cyano-4-fluoro-2-methylphenyl)-2-hydroxyethyl)-3-(hydroxymethyl)piperazine-1-carboxylate (synthesis described above, 0.090 g, 0.23 mmol) was dissolved in THF (2.3 mL) and cooled to 0° C. Triethylamine (0.038 mL, 0.274 mmol) was added followed by addition of Ms-Cl (0.020 mL, 0.252 mmol), and DMAP (2.79 mg, 0.023 mmol). The ice bath was removed and stirring was continued for 2 hours. The reaction mixture was then concentrated under reduced pressure. The resulting material was re-dissolved in DMSO (2 mL) and treated with potassium thioacetate (0.035 g, 0.306 mmol). The reaction mixture was stirred at room temperature under nitrogen overnight and then heated at 45° C. for 2 h. The mixture was diluted with ethyl acetate and washed with water (3 times) and brine, dried (Na2SO4), filtered and concentrated. The crude product was purified by column chromatography (100% hexane to 80% EtOAc/Hexane) to give the desired product LC/MS: M+1=452.3.

1. customThe ice bath was removed
2. concentrationThe reaction mixture was then concentrated under reduced pressure
3. dissolutionThe resulting material was re-dissolved in DMSO (2 mL)
4. stirringThe reaction mixture was stirred at room temperature under nitrogen overnight
5. temperatureheated at 45° C. for 2 h
6. washwashed with water (3 times) and brine
7. dry with materialdried (Na2SO4)
8. filtrationfiltered
9. concentrationconcentrated
10. customThe crude product was purified by column chromatography (100% hexane to 80% EtOAc/Hexane)