反应详情

温度

-20 °C

tert-Butyl 4-((5R,7R)-7-hydroxy-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)piperazine-1-carboxylate (1.190 g, 3.558 mmol) was dissolved in methylene chloride (55 mL) and cooled to −20° C. The solution was treated with DAST (1.410 mL, 10.68 mmol) and stirred at −20° C. for 1 hour. The reaction was quenched with ice and then warmed to ambient temperature. The mixture was diluted with saturated NH4Cl and separated. The aqueous phase was extracted with methylene chloride (2×), and the combined organics were dried over Na2SO4 and concentrated to a dark oil. This oil was chromatographed on SiO2 (Biotage 40S, load with methylene chloride) then eluted with 2.5% MeOH/DCM then 3.5% MeOH/DCM. The mixed fractions were concentrated, and the material was re-chromatographed on SiO2 (Biotage 40S, load with DCM) and eluted with 2 hexane/EtOAc. The product was collected as a dark oil to give tert-butyl 4-((5R,7S)-7-fluoro-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)piperazine-1-carboxylate (0.725 g, 61%). LCMS (APCI+) m/z 337.0 [M+H]+; Rf 3.13 min.

1. customThe reaction was quenched with ice
2. temperaturewarmed to ambient temperature
3. additionThe mixture was diluted with saturated NH4Cl
4. customseparated
5. extractionThe aqueous phase was extracted with methylene chloride (2×)
6. dry with materialthe combined organics were dried over Na2SO4
7. concentrationconcentrated to a dark oil
8. customThis oil was chromatographed on SiO2 (Biotage 40S, load with methylene chloride)
9. washthen eluted with 2.5% MeOH/DCM
10. concentrationThe mixed fractions were concentrated
11. customthe material was re-chromatographed on SiO2 (Biotage 40S, load with DCM)
12. washeluted with 2 hexane/EtOAc
13. customThe product was collected as a dark oil