反应详情

(rac.)-(1R*,5S*)-7-{4-[2-(2,6-Dichloro-4-methyl-phenoxy)-ethyl]-phenyl}-3,9-diaza-bicyclo[3.3.1]non-6-ene-3,6,9-tricarboxylic acid 3,9-di-tert-butyl ester (300 mg, 0.463 mmol) was dissolved in toluene (10 if L). DMF (1.8 μL) and oxalyl chloride (52.7 μl, 0.6 mmol) were added. The mixture was stirred at rt for 1 h. The solvents were thoroughly removed under reduced pressure, and the residue was dissolved in CH2Cl2 (7.5 μL). A sol. of [2-chloro-5-(3-methoxy-propyl)-benzyl]-cyclopropyl-amine (176 mg, 0.693 mmol) and Et3N (97 μL, 0.693 mmol) in CH2Cl2 (7.5 mL) was added over 10 min, then the mixture was stirred for 30 min. The mixture was evaporated and the residue was partitioned between Et2O and aq. 1M HCl. The org. fraction was washed with aq. sat. NaHCO3, and brine. The org. layer was dried over MgSO4, filtered, and the solvents were removed under reduced pressure. A sol. of this residue (402 mg, 0.455 mmol) and NaOEt (21% in EtOH, 0.257 mL, 0.683 mmol) in EtOH (2.84 mL) was heated at 80° C. overnight. The mixture was evaporated under reduced pressure, and the residue was dissolved in Et2O. This mixture was washed with aq. 1M HCl, aq. sat. NaHCO3, and brine. The org. layer was dried over MgSO4, filtered, and the solvents were removed under reduced pressure. Purification of the residue by FC yielded the title compound (300 mg).

1. customThe solvents were thoroughly removed under reduced pressure
2. dissolutionthe residue was dissolved in CH2Cl2 (7.5 μL)
3. stirringthe mixture was stirred for 30 min
4. customThe mixture was evaporated
5. customthe residue was partitioned between Et2O and aq. 1M HCl
6. washfraction was washed with aq. sat. NaHCO3, and brine
7. dry with materiallayer was dried over MgSO4
8. filtrationfiltered
9. customthe solvents were removed under reduced pressure
10. customThe mixture was evaporated under reduced pressure
11. dissolutionthe residue was dissolved in Et2O
12. washThis mixture was washed with aq. 1M HCl, aq. sat. NaHCO3, and brine
13. dry with materiallayer was dried over MgSO4
14. filtrationfiltered
15. customthe solvents were removed under reduced pressure
16. customPurification of the residue by FC