Phosphorus oxybromide → (+/-)-2,4-Dichloro-5-(1-bromoethyl)-pyrimidine

HRID 2216956Notes

Reaction equation

HRID 2216956 reaction equation
[Cl:1][C:2]1[N:7]=[C:6]([Cl:8])[C:5]([CH:9](O)[CH3:10])=[CH:4][N:3]=1.C(N(C(C)C)CC)(C)C.P(Br)(Br)([Br:23])=O>BrCBr.C(OCC)(=O)C.O>[Cl:1][C:2]1[N:7]=[C:6]([Cl:8])[C:5]([CH:9]([Br:23])[CH3:10])=[CH:4][N:3]=1

Participants

7

Reactant 3

HCID 24613Phosphorus oxybromideHCID 81531DiisopropylethylamineHCID 151416481-(2,4-Dichloropyrimidin-5-yl)ethan-1-ol

Product 1

HCID 21908975(+/-)-2,4-Dichloro-5-(1-bromoethyl)-pyrimidine

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 3024DibromomethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of (±)-1-(2,4-dichloro-pyrimidin-5-yl)-ethanol (0.50 g; 2.60 mmol) (from Example 1a supra) and diisopropylethylamine (1.10 mL; 6.25 mmol) (Aldrich) in dibromomethane (0.35 mL) was cooled to 15° C. Phosphorus oxybromide (0.73 g; 2.83 mmol) was added in one portion. Cooling bath was removed and reaction mixture was stirred at room temperature. After 20 minutes, the reaction was diluted with ethyl acetate and water. The organic phase was washed with brine and then dried over anhydrous sodium sulfate, filtered and concentrated to give crude (±)-2,4-dichloro-5-(1-bromoethyl)-pyrimidine (0.61 g; 91.4%). Purification by flash chromatography (Biotage, 40M, 10:90 ethyl acetate-hexanes) gave pure (±)-2,4-dichloro-5-(1-bromoethyl)-pyrimidine as an oil which solidified when stored in refrigerator.

Workup

  1. temperatureCooling bath
  2. customwas removed
  3. customreaction mixture
  4. washThe organic phase was washed with brine
  5. dry with materialdried over anhydrous sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customto give crude (±)-2,4-dichloro-5-(1-bromoethyl)-pyrimidine (0.61 g; 91.4%)
  9. customPurification by flash chromatography (Biotage, 40M, 10:90 ethyl acetate-hexanes)

Sources & evidence

ORD record
ord-ca09cc7671314b04bf540b7c76be502d
Source dataset
uspto-grants-2006_09
Patent number
US07112676B2

Reaction notes

Loading…