2,6-Dimethylphenol → HCID 28972704, compound

HRID 1469000Notes

Reaction equation

HRID 1469000 reaction equation
[CH3:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([CH3:8])[C:3]=1[OH:9].[F:10][C:11]1[CH:12]=[C:13]([N+:18]([O-])=O)[CH:14]=[CH:15][C:16]=1F.C([O-])([O-])=O.[K+].[K+].S([O-])([O-])(=O)=O.[Na+].[Na+]>[Zn].CCOC(C)=O.CS(C)=O>[F:10][C:11]1[CH:12]=[C:13]([CH:14]=[CH:15][C:16]=1[O:9][C:3]1[C:4]([CH3:8])=[CH:5][CH:6]=[CH:7][C:2]=1[CH3:1])[NH2:18]

Participants

8

Reactant 4

HCID 113352,6-DimethylphenolHCID 11430Potassium CarbonateHCID 24436Sodium SulfateHCID 1230531,2-Difluoro-4-nitrobenzene

Product 1

HCID 28972704HCID 28972704, compoundYield 90%

Reagents, catalysts & solvents 3

HCID 23994ZincCatalystHCID 679Dimethyl SulfoxideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
80 °C

Procedure

Solid 2,6-dimethylphenol (42.4 g, 346 mmol) was added in portions to a stirred mixture of 3,4-difluoronitrobenzene (50.0 g, 314 mmol), K2CO3 (65.0 g, 138 mmol), and DMSO (500 mL). After the addition was complete, the mixture was heated to 80° C. for 8 h and then allowed to cool to rt. The mixture was poured into ice water, and the resulting precipitate was collected and dried. This material was dissolved in acetone (1 L), then 150 mL of saturated aqueous NH4Cl was added and the mixture was immersed in an ice bath with mechanical stirring. Solid Zn powder (204 g, 65.4 mmol) was added in portions at such a rate that the internal temperature of the reaction mixture did not rise above 20° C. Following completion of the addition, the mixture was allowed to warm to rt and stirring was maintained for 6 h. EtOAc (ethyl acetate) (1.5 L) and anhydrous sodium sulfate (500 g) were added, and stirring was continued for 30 min. The mixture was then filtered though a pad of Celite®, rinsing well with EtOAc, and the filtrate was concentrated. The residue was triturated with hexanes to afford a solid (64.5 g, 90%). 1H NMR (400 MHz, CDCl3): 7.10-6.99 (m, 3H), 6.55 (ddd, J=12.5, 2.1, 0.8 Hz, 1H), 6.25-6.19 (m, 2H), 3.50 (s, 2H), 2.15 (s, 6H).

Workup

  1. additionAfter the addition
  2. temperatureto cool to rt
  3. customthe resulting precipitate was collected
  4. customdried
  5. dissolutionThis material was dissolved in acetone (1 L)
  6. addition150 mL of saturated aqueous NH4Cl was added
  7. customthe mixture was immersed in an ice bath with mechanical stirring
  8. customdid not rise above 20° C
  9. additioncompletion of the addition
  10. temperatureto warm to rt
  11. temperaturewas maintained for 6 h
  12. stirringstirring
  13. filtrationThe mixture was then filtered though a pad of Celite®
  14. washrinsing well with EtOAc
  15. concentrationthe filtrate was concentrated
  16. customThe residue was triturated with hexanes

Sources & evidence

ORD record
ord-9aee7bfef02e4a6faf088e82bc667780
Source dataset
uspto-grants-2015_04
Patent number
US09006251B2

Reaction notes

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