Réaction #10156

Équation de réaction

Triethylamine

methyl 3-bromo-2-bromomethylbenzoate

L-glutamine t-butyl ester hydrochloride

→

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

Rendement 48.0%

Solvants

THF

Conditions de réaction

Traitement

1. 1
   TempératureThe mixture was heated
2. 2
   Températureto reflux for 18 hours
3. 3
   Autresolvent was removed
4. 4
   workup.DISSOLUTIONThe residue was dissolved in methylene chloride (100 mL)
5. 5
   Lavagewashed with water (2×80 mL), brine (80 mL)
6. 6
   Séchagedried (MgSO4)
7. 7
   AutreSolvent was removed
8. 8
   Autrethe residue was purified by chromatography (CH2Cl2:CH3OH 97.5:2.5)

Mode opératoire

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.

Source