反应详情

To a stirred solution of methyl 4-[(1-tert-butoxycarbonyl-2-pyrrolidinyl)methoxy]cyclohexane carboxylate (450 mg, 1.3 mmol) in CH2Cl2 (5.0 ml) was added TFA (5.0 ml) at 0° C. The reaction mixture was stirred at room temperature for 0.5 hr. The mixture was concentrated in vacuo. Sat. NaHCO3 was added to the residue, and extracted with CH2Cl2. The extract was washed with brine, dried over Na2SO4, and concentrated in vacuo. The crude product was used to the subsequent reaction without further purification. To a stirred solution of the crude product, 4-[N′-(2-methylphenyl)uredio]phenylacetic acid (375 mg, 1.3 mmol), HOBt (178 mg, 1.3 mmol), and triethylamine (550 ml, 3.9 mmol) in THF (6.0 ml) and MeCN (6.0 ml) was added EDC.HCl (380 mg, 1.9 mmol) at 0° C. The reaction mixture was stirred at room temperature for 16 hr, and concentrated in vacuo. Water was added to the residue, and extracted with EtOAc. The extract was washed with sat. NaHCO3, 2-M citric acid, and sat. NaHCO3, then dried over Na2SO4, and concentrated in vacuo. The residue was purified by column chromatography on silica gel with n-hexane-EtOAc (1:6, v/v) as eluent to give methyl 4-[[1-[4-[N′-(2-methylphenyl)ureido]phenylacetyl]-(2S)-pyrrolidinyl]methoxy]cyclohexanecarboxylate (520 mg, 78%) as a colorless oil. 1H-NMR (CDCl3) δ 1.30–2.40 (m, 13H), 2.21 (s, 3H), 3.30–3.80 (m, 7H), 3.65 (s, 3H), 4.10–4.30 (m, 1H), 6.90–7.20 (m, 8H), 7.40–7.70 (m, 2H).

1. concentrationThe mixture was concentrated in vacuo
2. additionSat. NaHCO3 was added to the residue
3. extractionextracted with CH2Cl2
4. washThe extract was washed with brine
5. dry with materialdried over Na2SO4
6. concentrationconcentrated in vacuo
7. customThe crude product was used to the subsequent reaction without further purification
8. stirringThe reaction mixture was stirred at room temperature for 16 hr
9. concentrationconcentrated in vacuo
10. additionWater was added to the residue
11. extractionextracted with EtOAc
12. washThe extract was washed with sat. NaHCO3, 2-M citric acid, and sat. NaHCO3
13. dry with materialdried over Na2SO4
14. concentrationconcentrated in vacuo
15. customThe residue was purified by column chromatography on silica gel with n-hexane-EtOAc (1:6, v/v) as eluent