Dimethylformamide → 4-Amino-2-[1-(ethoxy-4-methoxyphenyl)-3-hydroxybutyl]isoindoline-1,3-dione

HRID 1661750Notes

Reaction equation

HRID 1661750 reaction equation
Cl.[NH2:2][CH:3]([C:8]1[CH:13]=[CH:12][C:11]([O:14][CH3:15])=[C:10](OCC)[CH:9]=1)[CH2:4][CH:5]([OH:7])[CH3:6].[NH2:19][C:20]1[CH:35]=[CH:34][CH:33]=[C:22]2[C:23](N(C(OCC)=O)[C:26](=[O:27])[C:21]=12)=[O:24].C(N([CH2:41][CH3:42])CC)C.CN(C)C=[O:46]>>[NH2:19][C:20]1[CH:35]=[CH:34][CH:33]=[C:22]2[C:21]=1[C:26](=[O:27])[N:2]([CH:3]([C:8]1[CH:9]=[CH:10][C:11]([O:14][CH3:15])=[CH:12][C:13]=1[O:46][CH2:41][CH3:42])[CH2:4][CH:5]([OH:7])[CH3:6])[C:23]2=[O:24]

Participants

5

Reactant 4

HCID 6228DimethylformamideHCID 8471TriethylamineHCID 187583154-Amino-4-(3-ethoxy-4-methoxyphenyl)butan-2-ol hydrochlorideHCID 187583363-amino-N-ethoxycarbonylphthalimide

Product 1

HCID 187583214-Amino-2-[1-(ethoxy-4-methoxyphenyl)-3-hydroxybutyl]isoindoline-1,3-dioneYield 52%

Conditions

Temperature
85 °C

Procedure

A mixture of 4-amino-4-(3-ethoxy-4-methoxyphenyl)butan-2-ol hydrochloride (1.0 g, 3.63 mmol), 3-amino-N-ethoxycarbonylphthalimide (0.85 g, 3.63 mmol) and triethylamine (2.37 g, 3.63 mmol) in dimethylformamide (15 mL) was heated at 80-90° C. for 16 hours. The mixture was concentrated in vacuo and the residue was stirred with methylene chloride (10 mL). The mixture was filtered and the filtrate was concentrated and purified by chromatography (silica gel, methylene chloride:ethyl acetate 8:2) to give 4-amino-2-[1-(ethoxy-4-methoxyphenyl)-3-hydroxybutyl]isoindoline-1,3-dione as a white solid (0.72 g, 52%); 1H NMR (CDCl3) δ 7.41-7.35 (m, 1H), 7.11-7.05 (m, 3H), 6.83-6.80 (m, 2H), 5.54-5.48 (dd, J=4.1 and 11.8 Hz, 1H), 5.22 (s, 2H), 4.10 (q, 2H), 3.85 (s, 3H), 3.77 (m, 1H), 2.88-2.77 (m, 1H), 2.07-1.00 (m, 1H), 1.67 (s, 1H), 1.45 (t, 3H), 1.27 (d, 3H).

Workup

  1. concentrationThe mixture was concentrated in vacuo
  2. filtrationThe mixture was filtered
  3. concentrationthe filtrate was concentrated
  4. custompurified by chromatography (silica gel, methylene chloride:ethyl acetate 8:2)

Sources & evidence

ORD record
ord-5d0f9a61ba8c4c56b9f80310132f77fa
Source dataset
uspto-grants-2011_10
Patent number
US08030343B2

Reaction notes

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