反应详情

温度

0 °C

2-(1,4-Dimethylpiperazin-2-yl)ethanol (703 mg, 4.44 mmol) was dissolved in anhydrous THF (20 mL) and the stirred solution cooled to 0° C. before NaH (60% dispersion in mineral oil; 550 mg, 13.8 mmol) was added. The suspension was left to stir for 10 minutes. 4-Nitrophenyl 4-phenylpiperazine-1-carboxylate (Intermediate 2; 1.89 g, 5.77 mmol) was added to the reaction mixture, which was left to stir at room temperature for 3 hours. After this time the reaction was terminated by cooling the mixture to 0° C. and cautiously quenching with saturated aqueous NaHCO3 solution (50 mL). The THF was removed in vacuo and transferred to a separating funnel where the organic product was extracted with EtOAc (3×75 mL). The combined organic extracts were collected together and washed with saturated aqueous NaHCO3 solution (3×75 mL). The organic layer was dried (MgSO4), filtered and concentrated in vacuo to give a crude yellow slurry. The crude residue was purified by reverse phase column chromatography (LiChroprep RP-18, 40-63 μm, 460×26 mm (100 g), 30 mL/min, gradient 0% to 15% (over 70 min) to 100% (over 5 min) MeOH in water with 1% formic acid). De-salting (using K2CO3 in DCM), filtration and concentration in vacuo afforded 4-phenylpiperazine-1-carboxylic acid 2-(1,4-dimethylpiperazin-2-yl)ethyl ester (236 mg, 13%) as a dark yellow oil.

1. additionwas added
2. waitThe suspension was left
3. waitwas left
4. stirringto stir at room temperature for 3 hours
5. customAfter this time the reaction was terminated
6. customcautiously quenching with saturated aqueous NaHCO3 solution (50 mL)
7. customThe THF was removed in vacuo
8. customtransferred to a separating funnel
9. extractionwhere the organic product was extracted with EtOAc (3×75 mL)
10. customThe combined organic extracts were collected together
11. washwashed with saturated aqueous NaHCO3 solution (3×75 mL)
12. dry with materialThe organic layer was dried (MgSO4)
13. filtrationfiltered
14. concentrationconcentrated in vacuo
15. customto give a crude yellow slurry
16. customThe crude residue was purified by reverse phase column chromatography (LiChroprep RP-18, 40-63 μm, 460×26 mm (100 g), 30 mL/min, gradient 0% to 15% (over 70 min) to 100% (over 5 min) MeOH in water with 1% formic acid)
17. filtrationDe-salting (using K2CO3 in DCM), filtration and concentration in vacuo