5-Bromouracil → 5-bromo-1-[2-fluoro-6-(trifluoromethyl)benzyl]pyrimidine-2,4(1H,3H)-dione

HRID 347779

Reaction equation

HRID 347779 reaction equation
[Br:1][C:2]1[C:3](=[O:9])[NH:4][C:5](=[O:8])[NH:6][CH:7]=1.C/C(/O[Si](C)(C)C)=N\[Si](C)(C)C.[F:22][C:23]1[CH:30]=[CH:29][CH:28]=[C:27]([C:31]([F:34])([F:33])[F:32])[C:24]=1[CH2:25]Br>ClC(Cl)C>[Br:1][C:2]1[C:3](=[O:9])[NH:4][C:5](=[O:8])[N:6]([CH2:25][C:24]2[C:27]([C:31]([F:32])([F:34])[F:33])=[CH:28][CH:29]=[CH:30][C:23]=2[F:22])[CH:7]=1

Participants

5

Reactant 3

HCID 58025-BromouracilHCID 27375732-(Bromomethyl)-1-fluoro-3-(trifluoromethyl)benzeneHCID 6913588N,O-bis(trimethylsilyl)acetamide

Product 1

HCID 220645015-bromo-1-[2-fluoro-6-(trifluoromethyl)benzyl]pyrimidine-2,4(1H,3H)-dioneYield 68.3%

Reagents, catalysts & solvents 1

HCID 63651,1-DichloroethaneSolvent

Procedure

A suspension of 5-bromouracil (31.0 g) in 300 mL of dichloroethane is treated with N,O-bis(trimethylsilyl)acetamide (80 mL). The reaction mixture is heated under nitrogen. The solution is cooled to ambient temperature, 2-fluoro-6-(trifluoromethyl)benzyl bromide (50 g) is added and the reaction mixture is heated overnight under the nitrogen. The reaction is cooled, quenched with MeOH, and partitioned between dichloromethane and water. The organic layer is washed with brine, dried (sodium sulfate), and evaporated to give a solid. The crude product is triturated with ether, filtered, and washed with ether three times providing 40.7 g of 5-bromo-1-[2-fluoro-6-(trifluoromethyl)benzyl]pyrimidine-2,4(1H,3H)-dione 5a. MS (CI) m/z 366.0, 368.0 (MH+).

Workup

  1. temperatureThe reaction mixture is heated under nitrogen
  2. temperaturethe reaction mixture is heated overnight under the nitrogen
  3. temperatureThe reaction is cooled
  4. customquenched with MeOH
  5. custompartitioned between dichloromethane and water
  6. washThe organic layer is washed with brine
  7. dry with materialdried (sodium sulfate)
  8. customevaporated
  9. customto give a solid
  10. customThe crude product is triturated with ether
  11. filtrationfiltered
  12. washwashed with ether three times

Sources & evidence

ORD record
ord-baac2d0e89cc467fbd7997411d6b3829
Source dataset
uspto-grants-2007_02
Patent number
US07176211B2

Linked notes

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