5-Bromo-2-chloropyrimidine → 2-Chloro-5-cyclobutylpyrimidine

HRID 1676219Notes

Reaction equation

HRID 1676219 reaction equation
Br[C:2]1[CH:3]=[N:4][C:5]([Cl:8])=[N:6][CH:7]=1.[Br-].[CH:10]1([Zn+])[CH2:13][CH2:12][CH2:11]1>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.ClCCl>[Cl:8][C:5]1[N:4]=[CH:3][C:2]([CH:10]2[CH2:13][CH2:12][CH2:11]2)=[CH:7][N:6]=1

Participants

5

Reactant 2

HCID 6066655-Bromo-2-chloropyrimidineHCID 178419766HCID 178419766, compound

Product 1

HCID 665200122-Chloro-5-cyclobutylpyrimidineYield 36%

Reagents, catalysts & solvents 2

HCID 178418807HCID 178418807, compoundCatalystHCID 6344DichloromethaneSolvent

Procedure

To a 100 mL recovery flask containing 5-bromo-2-chloropyrimidine (816 mg, 4.22 mmol) was applied vacuum then placed under a nitrogen atmosphere. To the flask was added dichloromethane (3 mL), PdCl2(dppf)-CH2Cl2 (172 mg, 0.211 mmol) and then cyclobutylzinc(II) bromide (8.44 mL, 4.22 mmol, 1.3 M in THF) over 1-2 minutes. The reaction was quenched at 2 hours with 20 mL of saturated aqueous NH4Cl and 50 mL EtOAc. The organic layer was washed with 20 mL each of saturated aqueous NaHCO3 and then NaCl, dried with MgSO4, filtered and concentrated to 0.88 g of yellow oil containing some solids. This was purified by flash chromatography (5-10% EtOAc in hexanes) to yield product (253 mg, 1.50 mmol, 36%) as a faintly pale yellow liquid with some small amount of crystalline material. MS (ESI) 169.1 (M+1).

Workup

  1. customThe reaction was quenched at 2 hours with 20 mL of saturated aqueous NH4Cl and 50 mL EtOAc
  2. washThe organic layer was washed with 20 mL each of saturated aqueous NaHCO3
  3. dry with materialNaCl, dried with MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated to 0.88 g of yellow oil
  6. additioncontaining some solids
  7. customThis was purified by flash chromatography (5-10% EtOAc in hexanes)

Sources & evidence

ORD record
ord-ee0620b7b59a494e9a5bf6ea73050b9e
Source dataset
uspto-grants-2011_08
Patent number
US08003796B2

Reaction notes

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