反应 #468766

反应方程式

diethyl(S)-2-(4-aminophthalimido)glutarate

HCl

→

diethyl(S)-2-(5-amino-1-oxo-2-isoindolinyl)glutarate

收率 41.0%

溶剂

ethanol

反应条件

后处理

1. 1
   其他had reached −40° C
2. 2
   过滤The excess of Zn was filtered from the solution, 10% palladium on carbon (1.0 g)
3. 3
   workup.ADDITIONwas added
4. 4
   workup.STIRRINGthe solution shaken under hydrogen at (30-50 psi) overnight
5. 5
   其他The catalyst was removed by filtration through celite
6. 6
   浓缩the filtrate concentrated in vacuo
7. 7
   workup.ADDITIONThe residue was made basic by the addition of saturated NaHCO3 solution (˜300 ml)
8. 8
   萃取extracted with diethyl ether (3×100 ml)
9. 9
   干燥the ether extracts were dried (K2CO3)
10. 10
    浓缩concentrated in vacuo
11. 11
    其他The residue was absorbed onto silica gel (15 g)
12. 12
    其他purified by chromatography on silica gel (400 g)
13. 13
    洗涤eluting with ethyl acetate:methylene chloride (1:4)

实验过程

A solution of diethyl(S)-2-(4-aminophthalimido)glutarate (10.5 g, 30.2 mmol) in ethanol (150 ml) was cooled in an acetonitrile/CO2 bath. Concentrated HCl (25 ml) was added followed by 30 mesh granular Zn (10.5 g, 0.161 mole) (Fisher) when the internal temperature had reached −40° C. The reaction mixture was stirred 1.5 hours at this temperature and a further 1 hour at −10° C. The excess of Zn was filtered from the solution, 10% palladium on carbon (1.0 g) was added, and the solution shaken under hydrogen at (30-50 psi) overnight. The catalyst was removed by filtration through celite and the filtrate concentrated in vacuo. The residue was made basic by the addition of saturated NaHCO3 solution (˜300 ml), extracted with diethyl ether (3×100 ml), and the ether extracts were dried (K2CO3) and concentrated in vacuo. The residue was absorbed onto silica gel (15 g) and purified by chromatography on silica gel (400 g) eluting with ethyl acetate:methylene chloride (1:4) to give diethyl(S)-2-(5-amino-1-oxo-2-isoindolinyl)glutarate as a viscous oil (4.14 g). 1H NMR (DMSO-d6, 300 MHz) δ: 1.12 (t, J=7 Hz, 3H, 3H, ester CH3), 1.17 (t, J=7 Hz, 3H, ester CH3), 1.98-2.33 (m, 4H, glu CH2CH2), 3.92-4.03 (m, 2H, ester CH2), 4.11 (q, J=7 Hz, 2H, ester CH2), 4.26 (very strongly coupled AB pair, 2H, ArCH2N), 4.77-4.84 (m, 1H, glu CH), 5.83 (br s, 2H, NH2), 6.58-6.65 (m, 2H, Ar), 7.32 (d, J=8 Hz, 1H, Ar). Mass spectrum (CI—CH4): 335 (M+1, 100%). Anal. Calculated for C17H22N2O5: C, 61.07; H, 6.63; N, 8.38. Found: C, 60.93; H, 6.71; H, 8.30.

来源