反应详情

To a solution of E-4-fluorocinnamic acid (1.18 g, 7.10 mmol), which is commercially available from Sigma-Aldrich, and TBTU (3.42 g, 10.6 mmol) in DMF (50 mL) was added 1-isopropylpiperazine (1.12 mL, 7.81 mmol) at ambient temperature. The reaction was stirred for ca. 15.5 h before being concentrated under reduced pressure, wherein the crude residue was dissolved in EtOAc (70 mL) and partitioned with sat. aq. NaHCO3 (25 mL). The aq. layer was separated and further extracted with EtOAc (2×30 mL). The combined organic layers were then washed with sat. aq. NaHCO3 (2×20 mL) and brine (35 mL), then concentrated in vacuo. The resulting residue was subjected to flash chromatography (SiO2-40 g; gradient elution: 100% DCM for 5 min, then 0% to 2% MeOH/DCM over 5 min; hold for 5 min, 2% to 4% over 5 min, hold for 5 min, 4% to 10% over 5 min, hold 10% MeOH/DCM for 5 min at 40 mL/min) to give 1.58 g 10A (80% yield) as a pale orange solid. m/z (ES+) M+1=277.4; HPLC tR=1.50 min. 1H NMR (500 MHz, CDCl3) δ 7.62 (d, J=15.6 Hz, 1H), 7.50 (dd, J=8.9, 5.5 Hz, 2H), 7.11-6.99 (m, 2H), 6.80 (d, J=15.6 Hz, 1H), 3.85-3.54 (m, 4H), 2.73 (quintet, J=6.7 Hz, 1H), 2.55 (d, J=5.2 Hz, 4H), 1.05 (d, J=6.4 Hz, 6H).

1. concentrationbefore being concentrated under reduced pressure, wherein the crude residue
2. dissolutionwas dissolved in EtOAc (70 mL)
3. custompartitioned with sat. aq. NaHCO3 (25 mL)
4. customThe aq. layer was separated
5. extractionfurther extracted with EtOAc (2×30 mL)
6. washThe combined organic layers were then washed with sat. aq. NaHCO3 (2×20 mL) and brine (35 mL)
7. concentrationconcentrated in vacuo
8. washgradient elution
9. wait100% DCM for 5 min
10. wait0% to 2% MeOH/DCM over 5 min
11. waithold for 5 min
12. wait2% to 4% over 5 min
13. waithold for 5 min
14. wait4% to 10% over 5 min
15. customfor 5 min