Phenol → 3,5-Dichloro-4-(phenoxymethyl)-2-pyridinamine

HRID 1370596Notes

Reaction equation

HRID 1370596 reaction equation
[C:1]1([OH:7])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[H-].[Na+:9].CN(C=O)C.[Cl:15][C:16]1[C:17]([NH2:25])=[N:18][CH:19]=[C:20]([Cl:24])[C:21]=1[CH2:22]Cl>C1COCC1.O>[O-:7][C:1]1[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[Na+:9].[Cl:15][C:16]1[C:17]([NH2:25])=[N:18][CH:19]=[C:20]([Cl:24])[C:21]=1[CH2:22][O:7][C:1]1[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1

Participants

8

Reactant 4

HCID 996PhenolHCID 6228DimethylformamideHCID 24758Sodium hydrideHCID 187528833,5-Dichloro-4-(chloromethyl)-2-pyridinamine

Product 2

HCID 4445035Phenolate SodiumHCID 187529073,5-Dichloro-4-(phenoxymethyl)-2-pyridinamineYield 83.3%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
60 °C

Procedure

Sodium phenoxide was prepared by the reaction of phenol (250 mg, 2.7 mmol) and sodium hydride (60% in oil, 106 mg, 2.7 mmol) in dry THF (15 ml) at RT. The solvent was removed in vacuo and replaced with dry DMF (10 ml), 3,5-dichloro-4-(chloromethyl)-2-pyridinamine (300 mg, 1.2 mmol) was added and the mixture heated to 60° C. for 2.5 h. After cooling to RT, the reaction mixture was diluted with water (15 ml) and extracted with diethyl ether (4×15 ml). The combined ethereal extracts were washed with water and saturated brine, dried over MgSO4, then concentrated to a solid. This was crystallised from methylene chloride and hexane to give the title compound as a white solid (219 mg+2nd crop of 45 mg, 1.0 mmol):

Workup

  1. customThe solvent was removed in vacuo
  2. additionwas added
  3. temperatureAfter cooling to RT
  4. extractionextracted with diethyl ether (4×15 ml)
  5. washThe combined ethereal extracts were washed with water and saturated brine
  6. dry with materialdried over MgSO4
  7. concentrationconcentrated to a solid
  8. customThis was crystallised from methylene chloride and hexane

Sources & evidence

ORD record
ord-48e9af8163234af099037b4971bc4e79
Source dataset
uspto-grants-2003_06
Patent number
US06583162B1

Reaction notes

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