反应详情

A solution of 1,3-dihydro-1-phenyl-3-(4-pyridinylmethyl)-2H-indol-2-one hydrochloride (33.7 g, 0.1 mol) in 200 ml CH2Cl2 was treated with 150 ml 1N NaOH. The organic phase was washed with water and brine, dried over anhydrous MgSO4, filtered, and concentrated to an oil which solidified on cooling. The "free base" was dissolved in 150 ml dry THF, cooled in an ice bath, treated with Nail (2.88 g, 0.12 mol), and stirred under dry nitrogen for 30 min. The mixture was treated with ethyl 4-bromobutyrate (19.5 g, 0.1 mol) in 25 ml dry THF. The mixture was stirred in the ice for 1 h and 16 h at room temperature. The reaction mixture was concentrated in vacuo, and the residue was partitioned between 300 ml Et2O and 200 ml water. The organic phase was washed with water and brine, dried over anhydrous MgSO4, filtered, treated with 150 ml 1N HCl-Et2O, and concentrated in vacuo. The residue was dissolved in 100 ml anhydrous EtOH with warming and stirred at room temperature for 24 h. The resulting crystals were collected by filtration, washed with a small portion of cold EtOH and Et2O, and dried in vacuo at 80° C. to give the desired product in 86% (38.6 g) yield; mp 182.5°-183.0° C.; IR(nujol): C=O @1722 and 1703 cm-1 ; NMR(DMSOd6TMS: δ1.15 (t, 3H, CH3), 1.2, 1.3 (2m, 2H, CH2CCCO), 2.1 (m, 2H, CH2CCO), 2.26 (t, 2H, CH2CO), [3.43 (d, 1H, J12), 3.64 (d, 1H, J12) CH2 -Pyr], 4.02 (q 2H, OCH2), [6.54 (m, 1H), 7.2 (m, 2 H), 7.5 (m, 5H), 7.68 (m, 1H) Ar--N-Phe], [7.10 (d, 2H), 8.70 (d, 2H) 4-Pyr]; Anal calcd for C26H26N2O3HCl, MW 450.97: C, 69.25; H, 6.04; N, 6.21. Found: C, 69.02; H, 5.98; N, 6.52. Mass spec m/e 415(M+1-HCl).

1. washThe organic phase was washed with water and brine
2. dry with materialdried over anhydrous MgSO4
3. filtrationfiltered
4. concentrationconcentrated to an oil which
5. temperatureon cooling
6. dissolutionThe "free base" was dissolved in 150 ml dry THF
7. temperaturecooled in an ice bath
8. additiontreated with Nail (2.88 g, 0.12 mol)
9. concentrationThe reaction mixture was concentrated in vacuo
10. customthe residue was partitioned between 300 ml Et2O and 200 ml water
11. washThe organic phase was washed with water and brine
12. dry with materialdried over anhydrous MgSO4
13. filtrationfiltered
14. additiontreated with 150 ml 1N HCl-Et2O
15. concentrationconcentrated in vacuo
16. dissolutionThe residue was dissolved in 100 ml anhydrous EtOH
17. temperaturewith warming
18. stirringstirred at room temperature for 24 h
19. filtrationThe resulting crystals were collected by filtration
20. washwashed with a small portion of cold EtOH and Et2O
21. customdried in vacuo at 80° C.