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

HRID 1039884Notes

Reaction equation

HRID 1039884 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+]>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.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

6

Reactant 3

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

Product 1

HCID 249019152-Chloro-4-cyclopropylpyrimidineYield 57.9%

Reagents, catalysts & solvents 2

HCID 178418807HCID 178418807, compoundCatalystHCID 8028TetrahydrofuranSolvent

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 round-bottom flask. THF (503 mL) was added and the suspension was heated to reflux with stifling 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 with stifling overnight
  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-6140402f37b64a3dbf0ce1af814567c1
Source dataset
uspto-grants-2013_10
Patent number
US08551984B2

Reaction notes

Loading…