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

HRID 433291Notes

Reaction equation

HRID 433291 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) δ7.41-7.35 (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-2f667475554e489db83dbdcaca96525b
Source dataset
uspto-grants-2003_12
Patent number
US06667316B1

Reaction notes

Loading…