Resorcinol → 3-((2-Chloropyrimidin-4-yl)oxy)phenol

HRID 643509Notes

Reaction equation

HRID 643509 reaction equation
[OH-].[Na+].[C:3]1([OH:10])[CH:8]=[CH:7][CH:6]=[C:5]([OH:9])[CH:4]=1.[Cl:11][C:12]1[N:17]=[C:16](Cl)[CH:15]=[CH:14][N:13]=1>O.CC(C)=O>[Cl:11][C:12]1[N:17]=[C:16]([O:9][C:5]2[CH:4]=[C:3]([OH:10])[CH:8]=[CH:7][CH:6]=2)[CH:15]=[CH:14][N:13]=1

Participants

6

Reactant 3

HCID 5054ResorcinolHCID 14798Sodium HydroxideHCID 775312,4-Dichloropyrimidine

Product 1

HCID 714221433-((2-Chloropyrimidin-4-yl)oxy)phenol

Reagents, catalysts & solvents 2

HCID 180AcetoneSolventHCID 962WaterSolvent

Conditions

Temperature
0 °C

Procedure

Sodium hydroxide (1.68 g; powder 98% pure; 40 mmol) is dissolved in water (30 mL), cooled to 0° C. and treated with benzene-1,3-diol (4.4 g; 40 mmol). Within 15 min, 2,4-dichloropyrimidine (5.95 g; 40 mmol) dissolved in acetone (50 mL) is added dropwise, keeping the reaction temperature below 5° C. After 15 min at 0° C., the ice bath is removed and the reaction kept stirring for additional 17.5 h. After filtering off the precipitate, the solvent is removed under reduced pressure. The residual oil is taken up into EtOAc, washed with sodium bicarbonate solution (10%), water and brine and dried over Na2SO4. After filtering, the crude product is isolated as an oil and purified by flash chromatography over silica gel (eluting with CH2Cl2/MeOH; 0-5%) to give the title compound of Stage 5.1 as a beige solid; ES-MS: [M+H]+; m/z=223; Rf (CH2Cl2/MeOH 9:1)=0.57; HPLC: AtRet=3.50 min.

Workup

  1. additionis added dropwise
  2. customthe reaction temperature below 5° C
  3. waitAfter 15 min at 0° C.
  4. customthe ice bath is removed
  5. filtrationAfter filtering off the precipitate
  6. customthe solvent is removed under reduced pressure
  7. washwashed with sodium bicarbonate solution (10%), water and brine
  8. dry with materialdried over Na2SO4
  9. filtrationAfter filtering
  10. customthe crude product is isolated as an oil
  11. custompurified by flash chromatography over silica gel (eluting with CH2Cl2/MeOH; 0-5%)

Sources & evidence

ORD record
ord-2396d7a3d7cb41b0afc1db5f2f978b12
Source dataset
uspto-grants-2010_04
Patent number
US07700605B2

Reaction notes

Loading…