反应详情

1-t-Butoxycarbonyl-3-oxopiperazine (21.6 g) is dissolved in dry DMF (500 ml) and potassium t-butoxide (24.2 g) is added. The mixture is stirred at 20–25° for 30 minutes, then 1-(4-methylphenylsulfonyloxy)-2-fluoroethane (J. Med. Chem., 23(9), 985–90 (1980), 25.9 g) is added and stirring continued at the same temperature for 24 hours. The solvent is to removed and the residue partitioned between ethyl acetate and water. The organic phase is washed with water and concentrated. The residue is dissolved in isopropanol and diluted with iso-hexane forming a precipitate which is removed by filtration. The mixture is chromatographed (silica; eluting with a gradient increasing in polarity from 0 to 50% isopropanol in iso-hexane) to give 1-t-butoxycarbonyl-4-(2-fluoroethyl)-3-oxopiperazine.

1. stirringstirring
2. waitcontinued at the same temperature for 24 hours
3. customto removed
4. customthe residue partitioned between ethyl acetate and water
5. washThe organic phase is washed with water
6. concentrationconcentrated
7. dissolutionThe residue is dissolved in isopropanol
8. additiondiluted with iso-hexane forming a precipitate which
9. customis removed by filtration
10. customThe mixture is chromatographed (silica
11. washeluting with
12. temperaturea gradient increasing in polarity from 0 to 50% isopropanol in iso-hexane)