Phosphorus tribromide → HCID 15735716, compound

HRID 2051240Notes

Reaction equation

HRID 2051240 reaction equation
P(Br)(Br)Br.[CH3:5][O:6][C:7](=[O:25])[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=1[NH:14][C:15]1[CH:20]=[CH:19][CH:18]=[C:17]([CH:21](O)[CH3:22])[C:16]=1[CH3:24].O1CCCCC1[O:32][NH2:33]>N1C=CC=CC=1.CN(C)C=O>[CH3:5][O:6][C:7](=[O:25])[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=1[NH:14][C:15]1[CH:20]=[CH:19][CH:18]=[C:17]([CH:21]([NH:33][OH:32])[CH3:22])[C:16]=1[CH3:24]

Participants

6

Reactant 3

HCID 24614Phosphorus tribromideHCID 5142091O-(Tetrahydropyran-2-yl)hydroxylamineHCID 15735715HCID 15735715, compound

Product 1

HCID 15735716HCID 15735716, compound

Reagents, catalysts & solvents 2

HCID 1049PyridineCatalystHCID 6228DimethylformamideSolvent

Procedure

Phosphorus tribromide (4.2 mL, 1 M solution in dichloromethane) is added dropwise to a solution of 2-[[3-(1-hydroxyethyl)-2-methylphenyl]amino]benzoic acid methyl ester (2.0 g, 7.0 mmol) and pyridine (2 drops) in dicholoromethane (50 mL) at 0° C. After the reaction mixture is stirred at room temperature for 1 hour, it is poured into a solution of O-tetrahydropyranylhydroxylamine (8.2 g, 70 mmol) in dimethylformamide (50 mL). The dichloromethane is evaporated under reduced pressure, and the reaction mixture is stirred overnight at room temperature. The reaction mixture is diluted with 200 mL water and extracted with 300 mL ether. The organic layer is washed with water and brine, and then evaporated to an oil. The crude intermediate THP-protected hydroxylamine is taken up in methanol and acidified with concentrated HCl to pH=1. The reaction mixture is heated at reflux for 30 minutes, cooled, and quenched by the careful addition of saturated aqueous sodium bicarbonate. The methanol is evaporated under reduced pressure and the product is extracted into ethyl acetate. The organic layer is washed with brine, dried over magnesium sulfate, and evaporated to give the crude hydroxylamine as an oil.

Workup

  1. customThe dichloromethane is evaporated under reduced pressure
  2. stirringthe reaction mixture is stirred overnight at room temperature
  3. additionThe reaction mixture is diluted with 200 mL water
  4. extractionextracted with 300 mL ether
  5. washThe organic layer is washed with water and brine
  6. customevaporated to an oil
  7. temperatureThe reaction mixture is heated
  8. temperatureat reflux for 30 minutes
  9. temperaturecooled
  10. customquenched by the careful addition of saturated aqueous sodium bicarbonate
  11. customThe methanol is evaporated under reduced pressure
  12. extractionthe product is extracted into ethyl acetate
  13. washThe organic layer is washed with brine
  14. dry with materialdried over magnesium sulfate
  15. customevaporated

Sources & evidence

ORD record
ord-1d5e565ff3d04c939b77027c1fce78b6
Source dataset
uspto-grants-1991_05
Patent number
US05017604

Reaction notes

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