3-Acetamidophthalic Anhydride → HCID 67417651, compound

HRID 913192Notes

Reaction equation

HRID 913192 reaction equation
C(O)(=O)C.[NH2:5][CH:6]([C:9]1[CH:14]=[CH:13][C:12]([O:15][CH3:16])=[C:11]([O:17][CH2:18][CH3:19])[CH:10]=1)[C:7]#[N:8].[C:20]([NH:23][C:24]1[CH:34]=[CH:33][CH:32]=[C:26]2[C:27]([O:29][C:30](=O)[C:25]=12)=[O:28])(=[O:22])[CH3:21]>C(O)(=O)C.CCOC(C)=O>[C:7]([CH:6]([C:9]1[CH:14]=[CH:13][C:12]([O:15][CH3:16])=[C:11]([O:17][CH2:18][CH3:19])[CH:10]=1)[N:5]1[C:30](=[O:29])[C:25]2[C:26](=[CH:32][CH:33]=[CH:34][C:24]=2[NH:23][C:20](=[O:22])[CH3:21])[C:27]1=[O:28])#[N:8]

Participants

5

Reactant 2

HCID 2261213-Acetamidophthalic AnhydrideHCID 67418487HCID 67418487, compound

Product 1

HCID 67417651HCID 67417651, compoundYield 85.3%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a mixture of 2-amino-2-(3-ethoxy-4-methoxyphenyl)ethanenitrile acetate (4.1 g, 14.6 mmol) and 3-acetamidophthalic anhydride (3.0 g, 14.6 mmol) in glacial acetic acid (60 mL), was heated to reflux for 17 hours. The mixture was concentrated in vacuo to provide an oil. The oil was dissolved in EtOAc and washed with water, brine and dried over MgSO4. Solvent was removed, and the residue was purified by chromatography (SiO2, Hexane:EtOAc 6:4) to give 4.9 g (83%) of N-{2-[cyano(3-ethoxy-4-methoxyphenyl)methyl]-1,3-dioxoisoindolin-4-yl}acetamide as a white solid; mp 118-120° C.; 1H NMR (CDCl3) δ 9.43 (s, 1H), 8.76 (d, J=8.4 Hz, 1H), 7.67 (t, J=7.7 Hz, 1H), 7.51 (d, J=7.2 Hz, 1H), 7.05-6.82 (m, 3H), 5.60-5.54 (dd, J=6.63 and 10.0 Hz, 1H), 4.10 (q, J=6.8 Hz, 2H), 3.81 (s, 3H), 3.81-3.74 (m, 1H), 3.29-3.20 (dd, J=6.2 and 16.8 Hz, 1H), 2.27 (s, 3H), 1.46 (t, J=7 Hz, 3H); 13C NMR (CDCl3) δ 169:56, 169.12, 167.19, 149.92, 148.64, 137.73, 136.30, 130.87, 128.70, 125.11, 119.92, 118.29, 116.76, 114.94, 112.14, 111.98, 64.56, 55.94, 51.08, 24.92, 21.04, 14.68. Aanly. Calculated for C22H21N3O5: C, 64.86; H, 5.20; N, 10.31. Found: C, 65.01; H, 5.10; N, 10.19.

Workup

  1. temperaturewas heated
  2. temperatureto reflux for 17 hours
  3. concentrationThe mixture was concentrated in vacuo
  4. customto provide an oil
  5. washwashed with water, brine
  6. dry with materialdried over MgSO4
  7. customSolvent was removed
  8. customthe residue was purified by chromatography (SiO2, Hexane:EtOAc 6:4)

Sources & evidence

ORD record
ord-587a7b9a0941491e996e84fe3c73303e
Source dataset
uspto-grants-2011_09
Patent number
US08026269B2

Reaction notes

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