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

HRID 10060Notes

Reaction equation

HRID 10060 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-c41d82aef6e44542b9d45c4257b7c152
Source dataset
uspto-grants-2006_08
Patent number
US07091353B2

Reaction notes

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