Acetic Anhydride → N-({2-[1-(3-ethoxy-4-methoxyphenyl)-2-(methylsulfonyl)ethyl]-1,3-dioxoisoindolin-4-yl}methyl)acetamide

HRID 1661772Notes

Reaction equation

HRID 1661772 reaction equation
[NH2:1][CH2:2][C:3]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:4]=1[C:5](=[O:30])[N:6]([CH:13]([C:19]1[CH:24]=[CH:23][C:22]([O:25][CH3:26])=[C:21]([O:27][CH2:28][CH3:29])[CH:20]=1)[CH2:14][S:15]([CH3:18])(=[O:17])=[O:16])[C:7]2=[O:12].[C:31](OC(=O)C)(=[O:33])[CH3:32]>>[CH2:28]([O:27][C:21]1[CH:20]=[C:19]([CH:13]([N:6]2[C:5](=[O:30])[C:4]3[C:8](=[CH:9][CH:10]=[CH:11][C:3]=3[CH2:2][NH:1][C:31](=[O:33])[CH3:32])[C:7]2=[O:12])[CH2:14][S:15]([CH3:18])(=[O:17])=[O:16])[CH:24]=[CH:23][C:22]=1[O:25][CH3:26])[CH3:29]

Participants

3

Reactant 2

HCID 7918Acetic AnhydrideHCID 116699704-(Aminomethyl)-2-[1-(3-ethoxy-4-methoxyphenyl)-2-methylsulfonylethyl]isoindoline-1,3-dione

Product 1

HCID 18758334N-({2-[1-(3-ethoxy-4-methoxyphenyl)-2-(methylsulfonyl)ethyl]-1,3-dioxoisoindolin-4-yl}methyl)acetamideYield 55%

Procedure

A stirred mixture of 4-(aminomethyl)-2-[1-(3-ethoxy-4-methoxyphenyl)-2-(methylsulfonyl)ethyl]isoindoline-1,3-dione (0.92 g, 2.13 mmol) and acetic anhydride (10 mL) was heated at reflux for 40 min and then cooled to room temperature. Excess acetic anhydride was removed in vacuo. The residue was dissolved in ethyl acetate (50 mL) and washed with 2N hydrogen chloride (20 mL), water (20 mL), brine (20 mL), and dried over magnesium sulfate. The solvent was removed in vacuo and the residue was purified by chromatography (silica gel, methylene chloride:ethyl acetate 75:25) to give N-({2-[1-(3-ethoxy-4-methoxyphenyl)-2-(methylsulfonyl)ethyl]-1,3-dioxoisoindolin-4-yl}methyl)acetamide (0.56 g, 55%) as a white solid: mp 84-86° C.; 1H NMR (CDCl3) δ 7.74-7.62 (m, 3H), 7.13-7.09 (m, 2H), 6.85-6.82 (m, 1H), 6.74-6.69 (m, 1H), 5.92-5.86 (dd, J=4.5, 10.1 Hz, 1H), 4.73 (d, J=6.3 Hz, 2H), 4.59-4.49 (dd, J=10.5, 14.2 Hz, 1H), 4.12 (q, J=6.8 Hz, 2H), 3.84 (s, 3H), 3.81-3.74 (m, 1H), 2.84 (s, 3H), 1.96 (s, 3H), 1.46 (t, J=6.9 Hz, 3H); 13C NMR (CDCl3) δ 170.15, 168.58, 167.77, 149.64, 148.54, 138.05, 135.38, 134.39, 132.07, 129.32, 128.21, 122.73, 120.40, 112.41, 111.37, 64.45, 55.88, 54.61, 48.65, 41.55, 39.42, 23.08, 14.62; Anal. Calcd. for C23H26N2O7S: C, 58.22; H, 5.52; N, 5.90; S, 6.76. Found: C, 57.87; H, 5.52; N, 5.65; S, 6.66.

Workup

  1. temperaturewas heated
  2. temperatureat reflux for 40 min
  3. customExcess acetic anhydride was removed in vacuo
  4. dissolutionThe residue was dissolved in ethyl acetate (50 mL)
  5. washwashed with 2N hydrogen chloride (20 mL), water (20 mL), brine (20 mL)
  6. dry with materialdried over magnesium sulfate
  7. customThe solvent was removed in vacuo
  8. customthe residue was purified by chromatography (silica gel, methylene chloride:ethyl acetate 75:25)

Sources & evidence

ORD record
ord-f32496ace0c0493fb4891d2d0e556c23
Source dataset
uspto-grants-2011_10
Patent number
US08030343B2

Reaction notes

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