Ammonium Chloride → 2-Chloro-4-(4-chlorophenyl)-6-cyclopropylpyrimidine

HRID 1989100Notes

Reaction equation

HRID 1989100 reaction equation
[Cl:1][C:2]1[N:7]=[C:6](Cl)[CH:5]=[C:4]([C:9]2[CH:14]=[CH:13][C:12]([Cl:15])=[CH:11][CH:10]=2)[N:3]=1.[Cl-].[CH:17]1([Zn+])[CH2:19][CH2:18]1.C1COCC1.C1([Mg]Br)CC1.C1COCC1.[NH4+].[Cl-]>C1COCC1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[Cl-].[Zn+2].[Cl-].C1COCC1>[Cl:1][C:2]1[N:3]=[C:4]([C:9]2[CH:14]=[CH:13][C:12]([Cl:15])=[CH:11][CH:10]=2)[CH:5]=[C:6]([CH:17]2[CH2:19][CH2:18]2)[N:7]=1

Participants

8

Reactant 4

HCID 25517Ammonium ChlorideHCID 11623053Pyrimidine, 2,4-dichloro-6-(4-chlorophenyl)-HCID 178420628HCID 178420628, compoundHCID 178420684HCID 178420684, compound

Product 1

HCID 574686162-Chloro-4-(4-chlorophenyl)-6-cyclopropylpyrimidineYield 42%

Reagents, catalysts & solvents 3

HCID 66790640zinc chloride THFCatalystHCID 178418397HCID 178418397, compoundCatalystHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 2,4-dichloro-6-(4-chloro-phenyl)-pyrimidine (2.6 g, 10.0 mmol) and tetrakis(triphenylphosphine)palladium (0.69 g, 0.6 mmol) in THF (10 mL) was added at 20° C. a 0.25 M cyclopropylzinc chloride/THF solution (120 mL, 30 mmol; freshly prepared by stirring a mixture of 60 mL of 0.5 M cyclopropylmagnesium bromide/THF and 60 mL of 0.5 M zinc chloride/THF for 1 h at 0° C., followed by 1 h at 20° C.) and the mixture was refluxed in an atmosphere of argon for 3 h. After the slow addition of sat. aqueous NH4Cl solution (20 mL) at 0° C. the mixture was partitioned between AcOEt and 10% sodium chloride solution. The organic layer was dried (Na2SO4) and evaporated in vacuo. The residue was chromatographed on silica gel using AcOEt/cyclohexane (1:19 v/v) as eluent to give 2-chloro-4-(4-chloro-phenyl)-6-cyclopropyl-pyrimidine (1.12 g, 42%) as a light yellow solid. MS (ISP) 265.1 [(M+H)+]; mp 70-72° C.

Workup

  1. customfreshly prepared
  2. temperature) and the mixture was refluxed in an atmosphere of argon for 3 h
  3. customwas partitioned between AcOEt and 10% sodium chloride solution
  4. dry with materialThe organic layer was dried (Na2SO4)
  5. customevaporated in vacuo
  6. customThe residue was chromatographed on silica gel

Sources & evidence

ORD record
ord-809fb29b9f34454b8b77b38bf9a65c40
Source dataset
uspto-grants-2010_01
Patent number
US07642264B2

Reaction notes

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