Tetrahydrofuran → 2-Chloro-4-cyclopropylpyrimidine

HRID 1028118Notes

Reaction equation

HRID 1028118 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>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].C(Cl)Cl.CCOC(C)=O>[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

7

Reactant 4

HCID 8028TetrahydrofuranHCID 62657Potassium Phosphate, TribasicHCID 775312,4-DichloropyrimidineHCID 2760897Cyclopropylboronic acid

Product 1

HCID 249019152-Chloro-4-cyclopropylpyrimidineYield 58%

Reagents, catalysts & solvents 2

HCID 178418807HCID 178418807, compoundCatalystHCID 8857Ethyl AcetateSolvent

Procedure

2,4-Dichloropyrimidine (15 g, 101 mmol), cyclopropylboronic acid (8.65 g, 101 mmol), PdCl2(dppf)-CH2Cl2 adduct (8.22 g, 10.07 mmol), and potassium phosphate (53.4 g, 252 mmol) were combined in a 1 L 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 sat 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 EtOAc/Hexanes to give 2-chloro-4-cyclopropylpyrimidine (10.124 g, 58.3 mmol, 58% yield) as an 89:11 mixture with EtOAc.

Workup

  1. temperaturethe suspension was heated
  2. temperatureto reflux
  3. concentrationconcentrated to −100 mL under reduced pressure
  4. extractionextracted with ethyl acetate
  5. washwashed
  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 EtOAc/Hexanes

Sources & evidence

ORD record
ord-0eae5335661748a4950b15686cf58fb2
Source dataset
uspto-grants-2014_05
Patent number
US08735417B2

Reaction notes

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