Ethyl Acetate → 2-[(4-chloro-3-hydroxyphenyl)methyl]-1H-isoindole-1,3(2H)-dione

HRID 1874760Notes

Reaction equation

HRID 1874760 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][N:9]2[C:17](=[O:18])[C:16]3[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=3)[C:10]2=[O:19])=[CH:4][C:3]=1[O:20]C.B(Br)(Br)Br.CCOC(C)=O>C(Cl)Cl>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][N:9]2[C:17](=[O:18])[C:16]3[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=3)[C:10]2=[O:19])=[CH:4][C:3]=1[OH:20]

Participants

5

Reactant 3

HCID 8857Ethyl AcetateHCID 25134Boron tribromideHCID 22467651HCID 22467651, compound

Product 1

HCID 594515952-[(4-chloro-3-hydroxyphenyl)methyl]-1H-isoindole-1,3(2H)-dioneYield 98.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

2-{[4-Chloro-3-(methyloxy)phenyl]methyl}-1H-isoindole-1,3(2H)-dione (7.0 g, 23 mmol) was dissolved in CH2Cl2 (25 mL) and cooled to 0° C. Boron tribromide (1.0 M solution, 46 mL) was added slowly then the solution was warmed to RT and stirred for 4 h. The reaction was cooled to 0° C. and ice water (100 mL) and EtOAc (200 mL) were added. The aqueous layer was separated and extracted with EtOAc (2×200 mL). The organic extracts were combined, dried over Na2SO4, filtered, evaporated and triturated with hexanes to afford the title compound (6.5 g, 97%) as a tan solid. 1H NMR (400 MHz, DMSO-d6): δ ppm 10.15 (s, 1H), 7.87 (d, 2H), 7.87 (ddd, 2H), 7.25 (d, 1H), 6.88 (d, 1H), 6.74 (dd, 1H), 4.66 (s, 2H). MS: m/z 286.0 (M−1).

Workup

  1. temperaturethe solution was warmed to RT
  2. temperatureThe reaction was cooled to 0° C.
  3. customThe aqueous layer was separated
  4. extractionextracted with EtOAc (2×200 mL)
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. customevaporated
  8. customtriturated with hexanes

Sources & evidence

ORD record
ord-f18565d4797643f2891a823e4d068744
Source dataset
uspto-grants-2012_11
Patent number
US08304419B2

Reaction notes

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