Methyl iodide → 3-Bromo-2-hydroxybenzonitrile

HRID 70283Notes

Reaction equation

HRID 70283 reaction equation
[C:1]([C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[OH:9])#[N:2].C(NC(C)C)(C)C.C1C(=O)N([Br:24])C(=O)C1.C([O-])([O-])=O.[K+].[K+].CI>C1(C)C=CC=CC=1.CCOC(C)=O.CN(C=O)C.O>[Br:24][C:5]1[C:4]([OH:9])=[C:3]([CH:8]=[CH:7][CH:6]=1)[C:1]#[N:2]

Participants

10

Reactant 5

HCID 6328Methyl iodideHCID 7912DiisopropylamineHCID 11430Potassium CarbonateHCID 119072-HydroxybenzonitrileHCID 67184N-bromobutanimide2×

Product 1

HCID 124686803-Bromo-2-hydroxybenzonitrile

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 1140TolueneSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

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.

Workup

  1. temperatureheating
  2. temperatureThe mixture was cooled
  3. washwashed (water, brine)
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated in vacuo
  6. customAttempted resolution of the two reaction products by flash chromatography (EtOAc/hexanes)
  7. additionthus the mixture of products
  8. stirringthe mixture was stirred overnight at room temperature
  9. extractionextracted with Et2O (×3)
  10. washCombined organics were washed (water, brine)
  11. dry with materialdried over Na2SO4
  12. concentrationconcentrated in vacuo
  13. customThe residue was purified by flash chromatography (EtOAc/hexanes)

Sources & evidence

ORD record
ord-0995036285214ab7a941ead28634dfc0
Source dataset
uspto-grants-2014_09
Patent number
US08822518B2

Reaction notes

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