Phthalic Anhydride → 2-[4-(4-Hydroxyphenyl)butyl]-1H-isoindole-1,3(2H)-dione

HRID 2218045Notes

Reaction equation

HRID 2218045 reaction equation
Br.[NH2:2][CH2:3][CH2:4][CH2:5][CH2:6][C:7]1[CH:12]=[CH:11][C:10]([OH:13])=[CH:9][CH:8]=1.[C:14]1(=O)[O:19][C:17](=[O:18])[C:16]2=[CH:20][CH:21]=[CH:22][CH:23]=[C:15]12.C(N(CC)CC)C>C(Cl)(Cl)Cl>[OH:13][C:10]1[CH:9]=[CH:8][C:7]([CH2:6][CH2:5][CH2:4][CH2:3][N:2]2[C:17](=[O:18])[C:16]3[C:15](=[CH:23][CH:22]=[CH:21][CH:20]=3)[C:14]2=[O:19])=[CH:12][CH:11]=1

Participants

5

Reactant 3

HCID 6811Phthalic AnhydrideHCID 8471TriethylamineHCID 115505224-(4-aminobutyl)phenol Hydrobromide

Product 1

HCID 220544512-[4-(4-Hydroxyphenyl)butyl]-1H-isoindole-1,3(2H)-dioneYield 41.4%

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent

Procedure

A mixture of 4-(4-aminobutyl)phenol hydrobromide 6 (8.2 g, 33.5 mmol), phthalic anhydride 7 (5.0 g, 33.8 mmol), and triethylamine (4.6 mL, 33.5 mmol) in chloroform (50 mL) was stirred at reflux for 18 h, cooled to room temperature and concentrated by rotary evaporation. The residue was dissolved in acetic acid (50 mL) and stirred at 100° C. for 3 h. Solvent was evaporated and the resulting residue was purified by flash silica gel column chromatography eluting with CH2Cl2/EtOAc/hexanes (8:1:1, v/v) to give the desired product 8 as a white powder (4.1 g, 41% yield). 1H NMR (300 MHz, DMSO-d6) δ 1.57 (m, 4H), 2.46 (m, 2H), 3.58 (m, 2H), 6.64 (d, 2H), 6.95 (d, 2H), 7.82 (m, 4H), 9.12 (s, 1H). m/z (ESI): 296 [C18H17NO3+H]+.

Workup

  1. temperatureat reflux for 18 h
  2. concentrationconcentrated by rotary evaporation
  3. dissolutionThe residue was dissolved in acetic acid (50 mL)
  4. stirringstirred at 100° C. for 3 h
  5. customSolvent was evaporated
  6. customthe resulting residue was purified by flash silica gel column chromatography
  7. washeluting with CH2Cl2/EtOAc/hexanes (8:1:1

Sources & evidence

ORD record
ord-d52071dd547d4e6ebb5acda2fb04174e
Source dataset
uspto-grants-2008_08
Patent number
US07410968B2

Reaction notes

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