Potassium Phosphate, Tribasic → 2-Chloro-4-cyclopropylpyrimidine

HRID 410394Notes

Reaction equation

HRID 410394 reaction equation
[Cl:1][C:2]1[N:7]=[C:6](Cl)[CH:5]=[CH:4][N:3]=1.[CH:9]1(B(O)O)[CH2:11][CH2:10]1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>C1COCC1>[Cl:1][C:2]1[N:7]=[C:6]([CH:9]2[CH2:11][CH2:10]2)[CH:5]=[CH:4][N:3]=1

Participants

5

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 775312,4-DichloropyrimidineHCID 2760897Cyclopropylboronic acid

Product 1

HCID 249019152-Chloro-4-cyclopropylpyrimidineYield 57.9%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

2,4-Dichloropyrimidine (15 g, 101 mmol), cyclopropylboronic acid (8.65 g, 101 mmol), Pda2(dppf)-CH2Cl2 adduct (8.22 g, 10.07 mmol), and potassium phosphate (53.4 g, 252 mmol) were combined in a 1 L round-bottom flask. THF (503 mL) was added and the suspension was heated to reflux with stirring overnight. The reaction was then cooled to room temperature, concentrated to ˜100 mL under reduced pressure, extracted with ethyl acetate, washed with saturated aqueous NaHCO3, brine, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel eluting with ethyl acetate in hexanes to give 2-chloro-4-cyclopropylpyrimidine (10.124 g, 58.3 mmol, 57.9%) as an 89:11 mixture of regioisomers.

Workup

  1. temperaturethe suspension was heated
  2. temperatureto reflux
  3. concentrationconcentrated to ˜100 mL under reduced pressure
  4. extractionextracted with ethyl acetate
  5. washwashed with saturated aqueous NaHCO3, brine
  6. dry with materialdried over anhydrous sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customThe residue was purified by column chromatography on silica gel eluting with ethyl acetate in hexanes

Sources & evidence

ORD record
ord-1ad78470599842e6afc3f45ab75b3285
Source dataset
uspto-grants-2014_06
Patent number
US08759366B2

Reaction notes

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