反応 #64643

反応方程式

ethyl 4-bromobutyrate

1,3-dihydro-1-phenyl-3-(4-pyridinylmethyl)-2H-indol-2-one hydrochloride

NaOH

→

desired product

2,3-Dihydro-2-oxo-1-phenyl-3-(4-pyridinylmethyl)-1H-indole-3-butanoic acid ethyl ester Hydrochloride

溶媒

THF

CH2Cl2

反応条件

後処理

1. 1
   洗浄The organic phase was washed with water and brine
2. 2
   乾燥dried over anhydrous MgSO4
3. 3
   ろ過filtered
4. 4
   濃縮concentrated to an oil which
5. 5
   温度on cooling
6. 6
   workup.DISSOLUTIONThe "free base" was dissolved in 150 ml dry THF
7. 7
   温度cooled in an ice bath
8. 8
   workup.ADDITIONtreated with Nail (2.88 g, 0.12 mol)
9. 9
   濃縮The reaction mixture was concentrated in vacuo
10. 10
    その他the residue was partitioned between 300 ml Et2O and 200 ml water
11. 11
    洗浄The organic phase was washed with water and brine
12. 12
    乾燥dried over anhydrous MgSO4
13. 13
    ろ過filtered
14. 14
    workup.ADDITIONtreated with 150 ml 1N HCl-Et2O
15. 15
    濃縮concentrated in vacuo
16. 16
    workup.DISSOLUTIONThe residue was dissolved in 100 ml anhydrous EtOH
17. 17
    温度with warming
18. 18
    workup.STIRRINGstirred at room temperature for 24 h
19. 19
    ろ過The resulting crystals were collected by filtration
20. 20
    洗浄washed with a small portion of cold EtOH and Et2O
21. 21
    その他dried in vacuo at 80° C.

実験手順

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).

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