2,6-Difluorophenol → HCID 136088166, compound

HRID 2282785Notes

Reaction equation

HRID 2282785 reaction equation
[CH3:1][O:2][CH2:3][CH2:4][O:5][CH2:6][CH2:7][O:8][CH2:9][CH2:10][O:11][C:12]1[CH:18]=[CH:17][C:15]([NH2:16])=[CH:14][CH:13]=1.[N:19]([O-])=O.[Na+].[F:23][C:24]1[CH:29]=[CH:28][CH:27]=[C:26]([F:30])[C:25]=1[OH:31]>O.Cl.[OH-].[K+]>[F:23][C:24]1[CH:29]=[C:28]([N:19]=[N:16][C:15]2[CH:14]=[CH:13][C:12]([O:11][CH2:10][CH2:9][O:8][CH2:7][CH2:6][O:5][CH2:4][CH2:3][O:2][CH3:1])=[CH:18][CH:17]=2)[CH:27]=[C:26]([F:30])[C:25]=1[OH:31]

Participants

7

Reactant 3

HCID 943922,6-DifluorophenolHCID 219176404-(2-(2-(2-Methoxyethoxy)ethoxy)ethoxy)anilineHCID 23668193Sodium Nitrite

Product 1

HCID 136088166HCID 136088166, compoundYield 14%

Reagents, catalysts & solvents 3

HCID 313Hydrochloric AcidSolvent2×HCID 962WaterSolventHCID 14797Potassium HydroxideSolvent

Procedure

4-(2-(2-(2-methoxyethoxy)ethoxy)ethoxy)aniline (17) (0.436 g, 1.71 mmol) was dissolved in hot mixture of 20 mL of water and 0.5 mL of conc. HCl. The solution was cooled in ice/NaCl bath to 0° C. and then the solution of sodium nitrite (0.140 g, 2.03 mmol in 4 mL of water) was added dropwise to the solution of ammonium salt, maintaining the temperature below +5° C. The resulting solution of diazonium salt was stirred for 30 min and then added dropwise to the solution of 2,6-difluorophenol (0.220 g, 1.69 mmol) in 10 mL of 1M KOH, cooled in ice/water bath. The reaction mixture was stirred for 40 min in ice/water bath and then acidified with 10% HCl to pH 2-3 and extracted with ethyl acetate (4×40 mL). The combined extract was washed with brine (30 mL), dried over Na2SO4 and evaporated. The crude product was purified by column chromatography on silica gel using 2:1 chloroform-ethyl acetate mixture as an eluant to give phenol 18 as a orange solid (0.094 g, 14%).

Workup

  1. temperaturemaintaining the temperature below +5° C
  2. extractionextracted with ethyl acetate (4×40 mL)
  3. extractionThe combined extract
  4. washwas washed with brine (30 mL)
  5. dry with materialdried over Na2SO4
  6. customevaporated
  7. customThe crude product was purified by column chromatography on silica gel using 2:1 chloroform-ethyl acetate mixture as an eluant

Sources & evidence

ORD record
ord-5e35af0753d54734ad2864e8cdc4d6e4
Source dataset
uspto-grants-2015_09
Patent number
US09140706B2

Reaction notes

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