Phenol → 4,5-Difluoro-6-phenoxypyrimidine

HRID 278379Notes

Reaction equation

HRID 278379 reaction equation
[C:1]1([OH:7])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.CC(C)([O-])C.[K+].[F:14][C:15]1[C:20]([F:21])=[C:19](F)[N:18]=[CH:17][N:16]=1>O1CCCC1>[O:7]([C:19]1[C:20]([F:21])=[C:15]([F:14])[N:16]=[CH:17][N:18]=1)[C:1]1[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1

Participants

5

Reactant 3

HCID 996PhenolHCID 35727644,5,6-TrifluoropyrimidineHCID 23665647Potassium tert-butoxide

Product 1

HCID 158696744,5-Difluoro-6-phenoxypyrimidineYield 68.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

At 0° C., a solution of 42.4 g (0.45 mol) of phenol and 50.4 g (0.45 mol) of potassium tert-butoxide in 400 ml of tetrahydrofuran is added dropwise to a solution of 80 g (0.6 mol) of 4,5,6-trifluoropyrimidine in 1 l of tetrahydrofuran. After the addition, the reaction mixture is stirred at 0° C. for 30 minutes and then poured onto water and extracted with ethyl acetate. The organic phase is dried over sodium sulphate and concentrated under reduced pressure and the residue is stirred with low-boiling petroleum ether. 63.8 g (68.1% of theory) of 4-phenoxy-5,6-difluoropyrimidine of melting point 65-66° C. are obtained.

Workup

  1. additionAfter the addition
  2. additionpoured onto water
  3. extractionextracted with ethyl acetate
  4. dry with materialThe organic phase is dried over sodium sulphate
  5. concentrationconcentrated under reduced pressure
  6. stirringthe residue is stirred with low-boiling petroleum ether

Sources & evidence

ORD record
ord-18e6c001fe5949668ae81d637b3da2ca
Source dataset
uspto-grants-2002_03
Patent number
US06359133B2

Reaction notes

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