1H-Isoindole-1,3(2H)-dione, 2-ethenyl- → {2-[2-(1.3-Dioxo-1,3-dihydro-isoindol-2-yl)-vinyl]-phenyl}-acetic acid

HRID 480360Notes

Reaction equation

C([O:5][C:6](=[O:15])[CH2:7][C:8]1[CH:13]=[CH:12][CH:11]=[C:10](Br)[CH:9]=1)(C)(C)C.[CH:16]([N:18]1[C:22](=[O:23])[C:21]2=[CH:24][CH:25]=[CH:26][CH:27]=[C:20]2[C:19]1=[O:28])=[CH2:17].C(N(C(C)C)CC)(C)C.C1(C)C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C>C(#N)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.CCOC(C)=O>[O:28]=[C:19]1[C:20]2[C:21](=[CH:24][CH:25]=[CH:26][CH:27]=2)[C:22](=[O:23])[N:18]1[CH:16]=[CH:17][C:13]1[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=1[CH2:7][C:6]([OH:5])=[O:15]

Participants

Conditions

Temperature: 90 °C

Procedure

A mixture of 3-bromo-phenyl acetic acid tert-butyl ester (5.64 g, 20.80 mmol), N-vinyl phthalimide (3.60 g, 20.80 mmol), diisopropylethylamine (3.63 g, 28.08 mmol), palladium acetate (107 mg, 0.478 mmol), and tritolylphosphine (475 mg, 1.56 mmol) in acetonitrile (10 mL) was stirred at 90° C. for 20 h. The reaction was cooled to room temperature and ice water (50 mL) was added. EtOAc (50 mL) was added and the organic solution was washed with 5.5% HCl followed by brine. The organic solution was dried over MgSO4, filtered, and concentrated. Purification by flash chromatography (hexanes:EtOAc 9:1 to 4:1) provided the title compound (1.95 g). MS 381 (M+18).

Workup

temperatureThe reaction was cooled to room temperature
washthe organic solution was washed with 5.5% HCl
dry with materialThe organic solution was dried over MgSO4
filtrationfiltered
concentrationconcentrated
customPurification by flash chromatography (hexanes:EtOAc 9:1 to 4:1)

Sources & evidence

ORD record: ord-69010a64655a4d408032c62f1cd36cf6
Source dataset: uspto-grants-2003_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06649657B2

Reaction notes

Loading…