Ethyl Acetate → 2-({[(4-Chloro-3-hydroxyphenyl)methyl]amino}carbonyl)benzoic acid

HRID 1874761Notes

Reaction equation

HRID 1874761 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.CC[O:28]C(C)=O>C(Cl)Cl>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][NH:9][C:17]([C:16]2[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=2[C:10]([OH:28])=[O:19])=[O:18])=[CH:4][C:3]=1[OH:20]

Participants

5

Reactant 3

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

Product 1

HCID 594516542-({[(4-Chloro-3-hydroxyphenyl)methyl]amino}carbonyl)benzoic acidYield 42%

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 sol., 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 and evaporated. The solid was dissolved in EtOAc and washed with 1N NaOH. The aqueous layers were combined, acidified with 10% citric acid and extracted with EtOAc. The organic extracts were combined, dried over Na2SO4, filtered and evaporated to afford the title compound (3.0 g, 42%) as a tan solid. 1H NMR (400 MHz, DMSO-d6): δ ppm 12.87 (br. s., 1H), 10.06 (s, 1H), 8.82 (t, 1H), 7.74 (d, 1H), 7.56 (dd, 1H), 7.47-7.54 (m, 1H), 7.45 (d, 1H), 7.23 (d, 1H), 6.94 (d, 1H), 6.80 (dd, 1H), 4.30 (d, 2H). MS: m/z 306.2 (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. dissolutionThe solid was dissolved in EtOAc
  9. washwashed with 1N NaOH
  10. extractionextracted with EtOAc
  11. dry with materialdried over Na2SO4
  12. filtrationfiltered
  13. customevaporated

Sources & evidence

ORD record
ord-02e27dd44921467790a960d72788ad92
Source dataset
uspto-grants-2012_11
Patent number
US08304419B2

Reaction notes

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