Water → 5-Bromo-2-phenoxypyrimidine

HRID 897465

Reaction equation

HRID 897465 reaction equation
[Br:1][C:2]1[CH:3]=[N:4][C:5](Cl)=[N:6][CH:7]=1.[C:9]1([OH:15])[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1.[OH-].[K+].O>C1(C)C=CC=CC=1.C1OCCOC2C(=CC=CC=2)OCCOCCOC2C(=CC=CC=2)OC1>[Br:1][C:2]1[CH:3]=[N:4][C:5]([O:15][C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)=[N:6][CH:7]=1

Participants

7

Reactant 4

HCID 962WaterHCID 996PhenolHCID 14797Potassium HydroxideHCID 6066655-Bromo-2-chloropyrimidine

Product 1

HCID 6428425-Bromo-2-phenoxypyrimidineYield 54.4%

Reagents, catalysts & solvents 2

HCID 26541Dibenzo-18-crown-6CatalystHCID 1140TolueneSolvent

Procedure

A mixture of 5-bromo-2-chloropyrimidine (5.00 g, 0.0259 mol), phenol (3.16 g, 0.0336 mol), dibenzo-18-Crown-6 (0.47 g, 0.0013 mol) and ground potassium hydroxide (3.51 g, 0.0626 mol) in toluene (75 ml) was heated at reflux for 5 hours with azeotropic removal of water. The mixture was allowed to cool to ambient temperature and the solvent was removed under reduced pressure. The residue was partitioned between water and chloroform. The layers were separated and the aqueous phase was extracted with chloroform three times. The combined organic layers were dried over magnesium sulfate, filtered and evaporated. The residue was purified by flash column chromatography on silica using n-heptane/ethyl acetate (98:2) as an eluent to give 5-bromo-2-phenoxy-pyrimidine as a white solid (3.55 g, 0.0141 mol): 1H NMR (DMSO-d6, 400 MHz) 8.80 (s, 2H), 7.45 (t, 2H), 7.27 (t, 1H), 7.22 (d 2H); TLC (n-heptane/ethyl acetate=95:5) Rf 0.20.

Workup

  1. temperaturewas heated
  2. customthe solvent was removed under reduced pressure
  3. customThe residue was partitioned between water and chloroform
  4. customThe layers were separated
  5. extractionthe aqueous phase was extracted with chloroform three times
  6. dry with materialThe combined organic layers were dried over magnesium sulfate
  7. filtrationfiltered
  8. customevaporated
  9. customThe residue was purified by flash column chromatography on silica

Sources & evidence

ORD record
ord-ece28418e4614288bf5fd0fd7c32b5ee
Source dataset
uspto-grants-2005_07
Patent number
US06921763B2

Linked notes

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