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

HRID 2282957Notes

Reaction equation

HRID 2282957 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) δ 9.54 (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, 1 H), 1.45 (t, J=7.0 Hz, 3H), 1.27 (d, J=6.3 Hz, 3H); 13C NMR (CDCl3) δ 170.36, 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-c3c29028c92a4b13be8f917ac481cf5e
Source dataset
uspto-grants-2015_09
Patent number
USRE045685E1

Reaction notes

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