Reaktion #157465

Reaktionsgleichung

NBS

o-cyanophenol

diisopropylamine

NBS

K2CO3

MeI

→

title compound

3-bromo-2-hydroxybenzonitrile

Lösungsmittel

EtOAc

PhMe

water

DMF

Reaktionsbedingungen

Aufarbeitung

1. 1
   Temperaturheating
2. 2
   TemperaturThe mixture was cooled
3. 3
   Waschenwashed (water, brine)
4. 4
   Trocknendried over Na2SO4
5. 5
   Einengenconcentrated in vacuo
6. 6
   SonstigeAttempted resolution of the two reaction products by flash chromatography (EtOAc/hexanes)
7. 7
   workup.ADDITIONthus the mixture of products
8. 8
   workup.STIRRINGthe mixture was stirred overnight at room temperature
9. 9
   Extraktionextracted with Et2O (×3)
10. 10
    WaschenCombined organics were washed (water, brine)
11. 11
    Trocknendried over Na2SO4
12. 12
    Einengenconcentrated in vacuo
13. 13
    SonstigeThe residue was purified by flash chromatography (EtOAc/hexanes)

Vorschrift

To a solution of o-cyanophenol (0.595 g; 5.00 mmol) and diisopropylamine (0.060 mL; 0.40 mmol) in PhMe (50 mL) at 70° C. was added NBS (0.980 g; 5.50 mmol) in one portion. The mixture was stirred 2 h, an additional portion of NBS (0.089 g; 0.5 mmol) was added and heating continued until disappearance of starting material was observed (TLC). The mixture was cooled, diluted with EtOAc washed (water, brine), dried over Na2SO4 and concentrated in vacuo. Attempted resolution of the two reaction products by flash chromatography (EtOAc/hexanes), was unsuccessful; thus the mixture of products was dissolved in DMF (10 mL), K2CO3 (2.07 g; 15.0 mmol) and MeI (0.47 mL; 7.5 mmol) were added and the mixture was stirred overnight at room temperature. The mixture was poured into water and extracted with Et2O (×3). Combined organics were washed (water, brine), dried over Na2SO4 and concentrated in vacuo. The residue was purified by flash chromatography (EtOAc/hexanes), affording the title compound as a colorless solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 3.97 (s, 3 H), 7.26 (app. t, J=7.9 Hz, 1 H), 7.86 (dd, J=7.8, 1.5 Hz, 1 H), 8.01 (dd, J=8.1, 1.5 Hz, 1 H). The product obtained above was combined with that of a similar reaction wherein N-methylbenzylamine (0.08 equiv) was substituted for the above diisopropylamine catalyst.

Quelle