Reaktion #10156

Reaktionsgleichung

Triethylamine

methyl 3-bromo-2-bromomethylbenzoate

L-glutamine t-butyl ester hydrochloride

→

tert-butyl 2-(4-bromo-1-oxoisoindolin-2-yl)-4-carbamoylbutanoate

Ausbeute 48.0%

Lösungsmittel

THF

Reaktionsbedingungen

Aufarbeitung

1. 1
   TemperaturThe mixture was heated
2. 2
   Temperaturto reflux for 18 hours
3. 3
   Sonstigesolvent was removed
4. 4
   workup.DISSOLUTIONThe residue was dissolved in methylene chloride (100 mL)
5. 5
   Waschenwashed with water (2×80 mL), brine (80 mL)
6. 6
   Trocknendried (MgSO4)
7. 7
   SonstigeSolvent was removed
8. 8
   Sonstigethe residue was purified by chromatography (CH2Cl2:CH3OH 97.5:2.5)

Vorschrift

Triethylamine (4.66 g, 46.09 mmol) was added to a stirred suspension of methyl 3-bromo-2-bromomethylbenzoate (6.45 g, 20.95 mmol) and L-glutamine t-butyl ester hydrochloride (5.0 g, 20.95 mmol) in THF (100 mL). The mixture was heated to reflux for 18 hours. The mixture was cooled to room temperature and solvent was removed. The residue was dissolved in methylene chloride (100 mL) and washed with water (2×80 mL), brine (80 mL) and dried (MgSO4). Solvent was removed and the residue was purified by chromatography (CH2Cl2:CH3OH 97.5:2.5) to afford tert-butyl 2-(4-bromo-1-oxoisoindolin-2-yl)-4-carbamoylbutanoate (3.97 g, 48%): 1H NMR (CDCl3) δ 7.74 (d, J=7.1 Hz, 1H), 7.65 (d, J=7.9 Hz, 1H), 7.35 (t, J=7.8 Hz, 1H), 6.15 (s, 1H), 5.77 (s, 1H), 5.02–4.96 (m, 1H), 4.58 (d, J=17.4 Hz, 1H), 4.34 (d, J=17.4 Hz, 1H), 2.45–2.10 (m, 4H), 1.46 (s, 9H); 13C NMR (CDCl3) δ 173.83, 169.42, 168.74, 142.28, 134.70, 133.65, 129.80, 122.70, 117.75, 82.66, 54.29, 47.80, 32.27, 27.95, 25.54.

Quelle