Sodium hydride → 4-Chloro-6-[1-(3,4-difluoro-phenyl)-2,2,2-trifluoro-ethoxy]-pyrimidine

HRID 1958588Notes

Reaction equation

HRID 1958588 reaction equation
[H-].[Na+].[F:3][C:4]1[CH:5]=[C:6]([CH:11]([OH:16])[C:12]([F:15])([F:14])[F:13])[CH:7]=[CH:8][C:9]=1[F:10].[Cl:17][C:18]1[CH:23]=[C:22](Cl)[N:21]=[CH:20][N:19]=1>C1COCC1>[Cl:17][C:18]1[CH:23]=[C:22]([O:16][CH:11]([C:6]2[CH:7]=[CH:8][C:9]([F:10])=[C:4]([F:3])[CH:5]=2)[C:12]([F:13])([F:14])[F:15])[N:21]=[CH:20][N:19]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 709434,6-DichloropyrimidineHCID 610879271-(3,4-Difluorophenyl)-2,2,2-trifluoroethanol

Product 1

HCID 866143024-Chloro-6-[1-(3,4-difluoro-phenyl)-2,2,2-trifluoro-ethoxy]-pyrimidineYield 70.8%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

NaH (80 mg, 60%, 3.0 mmol) was added to a solution of 1-(3,4-Difluoro-phenyl)-2,2,2-trifluoro-ethanol (212 mg, 1 mmol) in 5 ml of THF, the mixture was stirred for 20 minutes at room temperature. 4,6-Dichloro-pyrimidine (149 mg, 1 mmol) was added and then the reaction mixture was heated at 70° C. for 1 hour. After cooling, THF was evaporated. The residue was dissolved in 15 ml of EtOAc, and then washed with water, dried over sodium sulfate. The solvent was removed by rotovap to give 230 mg of 4-chloro-6-[1-(3,4-difluoro-phenyl)-2,2,2-trifluoro-ethoxy]-pyrimidine, yield 70%.

Workup

  1. temperaturethe reaction mixture was heated at 70° C. for 1 hour
  2. temperatureAfter cooling
  3. customTHF was evaporated
  4. dissolutionThe residue was dissolved in 15 ml of EtOAc
  5. washwashed with water
  6. dry with materialdried over sodium sulfate
  7. customThe solvent was removed by rotovap

Sources & evidence

ORD record
ord-b57ae8703f434f4ebbaba382f8349d1e
Source dataset
uspto-grants-2013_04
Patent number
US08410121B2

Reaction notes

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