反应详情

温度

-78 °C

To a stirred solution of oxalyl chloride (0.3 ml, 3.3 mmol) in CH2Cl2 (30.0 ml) was added DMSO (6.6 ml, 0.51 mmol) at −78° C. After 5 minutes, to the mixture was added 1-[3-methoxy-4-[N′-(2-methylphenyl)ureido]phenylacetyl]-2-pyrrolidinemethanol (1.2 g, 3.0 mmol) in CH2Cl2 (5.0 ml). The mixture was stirred for 30 minutes at −78° C., and triethylamine (2.1 ml, 15.0 mmol) was added. The mixture was stirred for 30 minutes at −78° C., and stirred for 30 minutes at room temperature. Water was added to the mixture, and extracted with CH2Cl2. The extract was washed with water, then 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, benzyl cis-4-aminocyclohexanecarboxylate (769 mg, 3.3 mmol), and AcOH (0.32 ml) in DCE (10 ml) was added NaBH(OAc)3 (1.1 g, 5.4 mmol) at 0° C. The reaction mixture was stirred at room temperature for 18 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 residue was purified by column chromatography on silica gel with MeOH—CH2Cl2 (1:9, v/v) as eluent to give benzylcis-4-[[1-[3-methoxy-4-[N′-(2-methylphenyl) ureido]phenylacetyl]-2-pyrrolidinyl]methylamino]cyclohexanecarboxylate (1.5 g, 83%) as an amorphous solid. 1H-NMR (CDCl3) δ 1.40–1.65 (m, 6H), 1.80–1.98 (m, 6H), 2.26 (s, 3H), 2.45–2.65 (m, 3H), 2.81–2.86 (m, 1H), 3.44–3.46 (m, 2H), 3.56 (s, 2H), 3.67 (s, 3H), 3.90–4.15 (m, 1H), 5.09 and 5.11 (each s, total 2H), 6.74–6.83 (m, 3H), 7.07–7.20 (m, 4H), 7.31–7.35 (m, 5H), 7.53–7.55 (m, 1H), 8.02–8.06 (m, 1H).

1. stirringThe mixture was stirred for 30 minutes at −78° C.
2. stirringstirred for 30 minutes at room temperature
3. extractionextracted with CH2Cl2
4. washThe extract was washed with water
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 18 hr
9. concentrationThe mixture was concentrated in vacuo
10. additionSat. NaHCO3 was added to the residue
11. extractionextracted with CH2Cl2
12. washThe extract was washed with brine
13. dry with materialdried over Na2SO4
14. concentrationconcentrated in vacuo
15. customThe residue was purified by column chromatography on silica gel with MeOH—CH2Cl2 (1:9, v/v) as eluent