Triethylamine → 1-(4-Nitro-1-oxoisoindolin-2-yl)propane-1,3-dicarboxylic acid dibenzyl ester

HRID 844226Notes

Reaction equation

HRID 844226 reaction equation
[N+:1]([C:4]1[C:5]([CH2:14]Br)=[C:6]([CH:11]=[CH:12][CH:13]=1)[C:7]([O:9]C)=O)([O-:3])=[O:2].C1(C)C=CC(S(O)(=O)=O)=CC=1.[CH2:27]([O:34][C:35](=[O:50])[C@H:36]([CH2:38][CH2:39][C:40]([O:42][CH2:43][C:44]1[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=1)=[O:41])[NH2:37])[C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1.C(N(CC)CC)C>C1COCC1.C(Cl)Cl>[CH2:27]([O:34][C:35]([CH:36]([N:37]1[CH2:14][C:5]2[C:6](=[CH:11][CH:12]=[CH:13][C:4]=2[N+:1]([O-:3])=[O:2])[C:7]1=[O:9])[CH2:38][CH2:39][C:40]([O:42][CH2:43][C:44]1[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=1)=[O:41])=[O:50])[C:28]1[CH:29]=[CH:30][CH:31]=[CH:32][CH:33]=1

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 1487795Methyl 2-(bromomethyl)-3-nitrobenzoateHCID 13233366L-Glutamic acid dibenzyl ester tosylate

Product 1

HCID 155498421-(4-Nitro-1-oxoisoindolin-2-yl)propane-1,3-dicarboxylic acid dibenzyl esterYield 59.5%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

A mixture of methyl 3-nitro-2-(bromomethyl)benzoate (2.5 g, 9.12 mmol), L-glutamic acid dibenzyl ester p-toluenesulfonate salt (3.0 g, 9.12 mmol) and triethylamine (2.0 g, 20.0 mmol) in THF (50 mL) is heated at reflux for 16 hours. The mixture is diluted with methylene chloride (150 mL) and washed with water (2×40 mL), brine (40 mL), dried and concentrated to an oil. The oil is purified by chromatography (silica gel, Hexane:ethoxyacetic acid 7:3) to give 1-(4-nitro-1-oxoisoindolin-2-yl)propane-1,3-dicarboxylic acid dibenzyl ester (2.65 g, 59%); 1H NMR (CDCl3) δ8.39 (d, J=7.8 Hz, 1H), 8.16 (d, J=7.3 Hz, 1H), 7.69 (t, J=7.9 Hz, 1H), 7.30 (m, 10H), 5.29 (s, 2H), 5.29-5.13 (m, 1H), 5.03 (s, 2H), 4.98 (d, J=19.1 Hz, 1H), 4.85 (d, J=19.2 Hz, 1H), 2.54-2.39 (m, 4H); 13C NMR (CDCl3) δ171.79, 169.92, 166.72, 143.47, 137.25, 135.49, 135.04, 134.99, 130.17, 129.67, 128.62, 128.52, 128.29, 128.25, 128.23, 127.04, 67.49, 66.58, 53.70, 48.35, 30.87, 24.79.

Workup

  1. temperatureis heated
  2. temperatureat reflux for 16 hours
  3. washwashed with water (2×40 mL), brine (40 mL)
  4. customdried
  5. concentrationconcentrated to an oil
  6. customThe oil is purified by chromatography (silica gel, Hexane:ethoxyacetic acid 7:3)

Sources & evidence

ORD record
ord-420a4f4a15cc4e03ad53b427e95fe004
Source dataset
uspto-grants-2002_04
Patent number
US06380239B1

Reaction notes

Loading…