Bromine → 6-(1-Bromoethyl)-2,4-dichloro-5-fluoropyrimidine

HRID 459416Notes

Reaction equation

HRID 459416 reaction equation
[Cl:1][C:2]1[N:7]=[C:6]([Cl:8])[C:5]([F:9])=[C:4]([CH2:10][CH3:11])[N:3]=1.[Br:12]N1C(=O)CCC1=O.BrBr>O>[Br:12][CH:10]([C:4]1[N:3]=[C:2]([Cl:1])[N:7]=[C:6]([Cl:8])[C:5]=1[F:9])[CH3:11]

Participants

5

Reactant 3

HCID 24408BromineHCID 67184N-bromobutanimide2×HCID 223233532,4-Dichloro-6-ethyl-5-fluoropyrimidine

Product 1

HCID 223233396-(1-Bromoethyl)-2,4-dichloro-5-fluoropyrimidineYield 95%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent2×

Procedure

A mixture of the compound of part (i) (400 g), N-bromosuccinimide (730 g), azoisobutyronitrile (33.7 g), bromine (65.5 g) and water (6.4 L) was heated at 80–85° C. for 5 hours. Further N-bromosuccinimide (183 g) was added, heating continued for 2 hours then further azoisobutyronitrile (33.7 g) added. After heating for 2 hours at 85° C. further azoisobutyronitrile (33.7 g) was added and heating continued for 3 hours. The reaction was cooled, diluted with water (4 L) and extracted with dichloromethane (2×3 L). The combined organic extracts were washed with a solution of sodium metabisulphate (600 g) in water (2.5 L), followed by water (3 L). The solvent was removed by evaporation under reduced pressure, toluene (1.0 L) added and the solution concentrated under reduced pressure to give the product as an oil (534 g).

Workup

  1. temperaturewas heated at 80–85° C. for 5 hours
  2. temperatureheating
  3. additionwas added
  4. temperatureheating
  5. waitcontinued for 3 hours
  6. temperatureThe reaction was cooled
  7. extractionextracted with dichloromethane (2×3 L)
  8. washThe combined organic extracts were washed with a solution of sodium metabisulphate (600 g) in water (2.5 L)
  9. customThe solvent was removed by evaporation under reduced pressure, toluene (1.0 L)
  10. additionadded
  11. concentrationthe solution concentrated under reduced pressure

Sources & evidence

ORD record
ord-fca3c9b202584e859da42c5504b3bb1d
Source dataset
uspto-grants-2007_03
Patent number
US07193083B2

Reaction notes

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