반응 #10156

반응 방정식

Triethylamine

methyl 3-bromo-2-bromomethylbenzoate

L-glutamine t-butyl ester hydrochloride

→

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

수율 48.0%

용매

THF

반응 조건

후처리

1. 1
   온도The mixture was heated
2. 2
   온도to reflux for 18 hours
3. 3
   기타solvent was removed
4. 4
   workup.DISSOLUTIONThe residue was dissolved in methylene chloride (100 mL)
5. 5
   세척washed with water (2×80 mL), brine (80 mL)
6. 6
   건조dried (MgSO4)
7. 7
   기타Solvent was removed
8. 8
   기타the residue was purified by chromatography (CH2Cl2:CH3OH 97.5:2.5)

실험 절차

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.

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