Triethylamine → N-(2-[1-(3-ethoxy-4-methoxyphenyl)-3-hydroxybutyl]-1,3-dioxoisoindolin-4-yl}acetamide

HRID 433289Notes

Reaction equation

HRID 433289 reaction equation
Cl.[NH2:2][CH:3]([C:8]1[CH:13]=[CH:12][C:11]([O:14][CH3:15])=[C:10]([O:16][CH2:17][CH3:18])[CH:9]=1)[CH2:4][CH:5]([OH:7])[CH3:6].[C:19]([NH:22][C:23]1[CH:33]=[CH:32][CH:31]=[C:25]2[C:26]([O:28][C:29](=O)[C:24]=12)=[O:27])(=[O:21])[CH3:20].C(N(CC)CC)C>CN(C)C=O>[CH2:17]([O:16][C:10]1[CH:9]=[C:8]([CH:3]([N:2]2[C:29](=[O:28])[C:24]3[C:25](=[CH:31][CH:32]=[CH:33][C:23]=3[NH:22][C:19](=[O:21])[CH3:20])[C:26]2=[O:27])[CH2:4][CH:5]([OH:7])[CH3:6])[CH:13]=[CH:12][C:11]=1[O:14][CH3:15])[CH3:18]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 2261213-Acetamidophthalic AnhydrideHCID 187583154-Amino-4-(3-ethoxy-4-methoxyphenyl)butan-2-ol hydrochloride

Product 1

HCID 18758319N-(2-[1-(3-ethoxy-4-methoxyphenyl)-3-hydroxybutyl]-1,3-dioxoisoindolin-4-yl}acetamideYield 65%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
85 °C

Procedure

A mixture of 4-amino-4-(3-ethoxy-4-methoxyphenyl)butan-2-ol hydrochloride (0.5 g, 1.81 mmol), 3-acetamidophthalic anhydride (0.37 g, 1.81 mmol) and triethylamine (0.18 g, 1.81 mmol) in dimethylformamide (10 mL) was heated at 80-90° C. for 7 hours. The mixture was concentrated in vacuo to an oil. The oil was dissolved in ethyl acetate, washed with water, brine, dried, filtered and concentrated to an oil. This oil was purified by chromatography (silica gel, methylene chloride/ethyl acetate 8:2) to give N-{2-[1-(3-ethoxy-4-methoxyphenyl)-3-hydroxybutyl]-1,3-dioxoisoindolin-4-yl}acetamide as a white solid (0.5 g, 65%); mp 132-134° C.; 1H NMR (CDCl3) δ9.54 (s, 1H), 8.73 (d, J=8.4 Hz, 1H), 7.62 (t, J=7.4 Hz, 1H), 7.46 d, J=7.3 Hz, 1H), 7.12-7.08 (m, 2H), 6.83 (d, J=8.0 Hz, 1H), 5.46 (t, J=7.8 Hz, 1H), 4.12 (q, J=7.1 Hz, 2H), 3.84 (s, 3H), 3.80 (m, 1H), 2.59-2.42 (m, 2H), 2.25 (s, 3H), 1.65 (s, 1H), 1.45 (t, J=7.0 Hz, 3H), 1.27 (d, J=6.3 Hz, 3H); 13C NMR (CDCl3) δ170.36, 169.20, 167.96, 149.04, 148.26, 137.29, 135.70, 131.50, 131.35, 124.60, 120.61, 117.85, 113.10, 111.25, 66.00, 64.39, 55.89, 52.43, 40.19, 24.92, 24.33, 14.73; Anal. Calcd. For C23H26N2O6: C, 64.78; H, 6.15; N, 6.57. Found: C, 64.86; H, 6.10; N, 6.46.

Workup

  1. concentrationThe mixture was concentrated in vacuo to an oil
  2. dissolutionThe oil was dissolved in ethyl acetate
  3. washwashed with water, brine
  4. customdried
  5. filtrationfiltered
  6. concentrationconcentrated to an oil
  7. customThis oil was purified by chromatography (silica gel, methylene chloride/ethyl acetate 8:2)

Sources & evidence

ORD record
ord-9f2d295544dc4b869a24197eef22615d
Source dataset
uspto-grants-2003_12
Patent number
US06667316B1

Reaction notes

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