Tetrahydrofuran → 2-Chloro-4-(4-fluorobenzyloxy)pyrimidine

HRID 15064

Reaction equation

HRID 15064 reaction equation
C([Li])CCC.O1CCCC1.[F:11][C:12]1[CH:19]=[CH:18][C:15]([CH2:16][OH:17])=[CH:14][CH:13]=1.[Cl:20][C:21]1[N:26]=[C:25](Cl)[CH:24]=[CH:23][N:22]=1>O>[Cl:20][C:21]1[N:26]=[C:25]([O:17][CH2:16][C:15]2[CH:18]=[CH:19][C:12]([F:11])=[CH:13][CH:14]=2)[CH:24]=[CH:23][N:22]=1

Participants

6

Reactant 4

HCID 8028Tetrahydrofuran2×HCID 680224-Fluorobenzylic alcoholHCID 775312,4-DichloropyrimidineHCID 178418339Butyllithium

Product 1

HCID 860707302-Chloro-4-(4-fluorobenzyloxy)pyrimidineYield 68%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

n-Butyl lithium (2.6 M n-hexane solution, 10.1 mL) was added to tetrahydrofuran solution (12 mL) of 4-fluorobenzyl alcohol (3.08 mL) at −78° C., and stirred at the same temperature for 30 minutes. This reaction liquid was gradually added to tetrahydrofuran suspension (24 mL) of 2,4-dichloropyrimidine (4.0 g) and stirred at room temperature for 2 hours. After addition of water, the reaction liquid was extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate. Concentrating the solvent under reduced pressure, the residue was crystallized from mixed solvent of chloroform and hexane to provide the title compound (4.36 g, 68%).

Workup

  1. customThis reaction liquid
  2. stirringstirred at room temperature for 2 hours
  3. customthe reaction liquid
  4. extractionwas extracted with ethyl acetate
  5. washThe organic layer was washed with saturated brine
  6. dry with materialdried over anhydrous magnesium sulfate
  7. concentrationConcentrating the solvent under reduced pressure
  8. customthe residue was crystallized
  9. additionfrom mixed solvent of chloroform and hexane

Sources & evidence

ORD record
ord-ab4bf3d2c4494cc991525056ab6da85b
Source dataset
uspto-grants-2010_06
Patent number
US07732456B2

Linked notes

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