反应详情

A mixture of methyl 4-[2-({[4-(2-tert-butylphenyl)piperazin-1-yl](oxo)acetyl}amino)ethyl]benzoate (Example 202, 0.51 g, 1.13 mmol) and 1 M LiOH solution (5 mL, 5.0 mmol) in tetrahydrofuran (5 mL) was stirred at room temperature for 1 h. Then to this mixture was added 8 M NaOH solution (5 mL, 40 mmol) and methanol (10 mL) and stirred at room temperature for 2 h. The reaction mixture was acidified with 1 M HCl solution and extracted with ethyl acetate. The extract was washed with brine, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane/ethyl acetate 70:30 to 0:100 then ethyl acetate/methanol 100/0 to 70/30) and HPLC (Gilson Preparative HPLC System; column: YMC Combiprep ODS-A, S-5 μm, 50×20 mm; solvent: A; water containing 0.1% TFA, B; acetonitrile containing 0.1% TFA; gradient cycle: 0.00 min (A/B=90/10), 1.00 min (A/B=90/10), 4.20 min (A/B=10/90), 5.40 min (A/B=10/90), 5.50 min (A/B=90/10), 5.60 min (A/B=90/10); flow rate: 25 mL/min; detect: UV 220 nm) to give the title compound (38 mg, 8%) as a yellow amorphous.

1. stirringstirred at room temperature for 2 h
2. extractionextracted with ethyl acetate
3. washThe extract was washed with brine
4. dry with materialdried over anhydrous magnesium sulfate
5. filtrationfiltered
6. concentrationconcentrated under reduced pressure
7. customThe residue was purified by silica gel column chromatography (hexane/ethyl acetate 70:30 to 0:100
8. custom0.00 min
9. custom1.00 min
10. custom4.20 min
11. custom5.40 min
12. custom5.50 min
13. custom5.60 min