Potassium Carbonate → 3-[2-(4-fluorophenoxy)ethoxy]-1-methyl-4-(4-methylphenyl)-1H-pyrazol-5-ylamine

HRID 1062791Notes

Reaction equation

HRID 1062791 reaction equation
[NH2:1][C:2]1[N:6]([CH3:7])[N:5]=[C:4]([OH:8])[C:3]=1[C:9]1[CH:14]=[CH:13][C:12]([CH3:15])=[CH:11][CH:10]=1.C(=O)([O-])[O-].[K+].[K+].[F:22][C:23]1[CH:32]=[CH:31][C:26]([O:27][CH2:28][CH2:29]Br)=[CH:25][CH:24]=1>CN(C)C=O>[F:22][C:23]1[CH:32]=[CH:31][C:26]([O:27][CH2:28][CH2:29][O:8][C:4]2[C:3]([C:9]3[CH:14]=[CH:13][C:12]([CH3:15])=[CH:11][CH:10]=3)=[C:2]([NH2:1])[N:6]([CH3:7])[N:5]=2)=[CH:25][CH:24]=1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 20641711-(2-Bromoethoxy)-4-fluorobenzeneHCID 1784239155-amino-1-methyl-4-(4-methylphenyl)-1H-pyrazol-3-ol

Product 1

HCID 234003123-[2-(4-fluorophenoxy)ethoxy]-1-methyl-4-(4-methylphenyl)-1H-pyrazol-5-ylamineYield 58.9%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To 5-amino-1-methyl-4-(4-methylphenyl)-1H-pyrazol-3-ol (Preparation 3a) (5 g) in dimethylformamide (30 ml) at room temperature was added potassium carbonate (24.8 g) and 4-fluorophenoxyethylbromide (5.6 g), the mixture was stirred for 16 hrs. The reaction was partitioned between water (100 ml) and diethyl ether (100 ml). The aqueous layer was separated and extracted with further diethyl ether (4×100 ml). The organic fractions were combined, washed with water, then brine, dried over magnesium sulfate, filtered, and concentrated under reduced pressure azeotroping with xylene. The residue was purified by column chromatography on silica gel eluting with a solvent gradient, pentane:ethylacetate (7:3 to 0:1, by volume) to yield the title compound as a white solid (4.95 g).

Workup

  1. customThe reaction was partitioned between water (100 ml) and diethyl ether (100 ml)
  2. customThe aqueous layer was separated
  3. extractionextracted with further diethyl ether (4×100 ml)
  4. washwashed with water
  5. dry with materialbrine, dried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customazeotroping with xylene
  9. customThe residue was purified by column chromatography on silica gel eluting with a solvent gradient, pentane:ethylacetate (7:3 to 0:1, by volume)

Sources & evidence

ORD record
ord-6df20195c08b4833a609213864cca7e8
Source dataset
uspto-grants-2005_11
Patent number
US06962923B2

Reaction notes

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