Triethylamine → Tert-butyl 2-(4-bromo-1-oxoisoindolin-2-yl)-4-carbamoylbutanoate

HRID 2103578Notes

Reaction equation

HRID 2103578 reaction equation
C(N(CC)CC)C.[Br:8][C:9]1[C:10]([CH2:19]Br)=[C:11]([CH:16]=[CH:17][CH:18]=1)[C:12]([O:14]C)=O.Cl.[C:22]([O:26][C:27](=[O:35])[C@H:28]([CH2:30][CH2:31][C:32](=[O:34])[NH2:33])[NH2:29])([CH3:25])([CH3:24])[CH3:23]>C1COCC1>[Br:8][C:9]1[CH:18]=[CH:17][CH:16]=[C:11]2[C:10]=1[CH2:19][N:29]([CH:28]([CH2:30][CH2:31][C:32](=[O:34])[NH2:33])[C:27]([O:26][C:22]([CH3:25])([CH3:23])[CH3:24])=[O:35])[C:12]2=[O:14]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 15602445H-Gln-OtBu hydrochlorideHCID 21907554Methyl 3-bromo-2-(bromomethyl)benzoate

Product 1

HCID 21988515Tert-butyl 2-(4-bromo-1-oxoisoindolin-2-yl)-4-carbamoylbutanoateYield 48%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

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.

Workup

  1. temperatureThe mixture was heated
  2. temperatureto reflux for 18 hours
  3. customsolvent was removed
  4. dissolutionThe residue was dissolved in methylene chloride (100 mL)
  5. washwashed with water (2×80 mL), brine (80 mL)
  6. dry with materialdried (MgSO4)
  7. customSolvent was removed
  8. customthe residue was purified by chromatography (CH2Cl2:CH3OH 97.5:2.5)

Sources & evidence

ORD record
ord-5edc02eee7e5422f9ed765054ce1940b
Source dataset
uspto-grants-2009_08
Patent number
US07576104B2

Reaction notes

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