N-methyl-2-pyrrolidone → 2-Chloro-6-methoxy-4-methylquinazoline

HRID 1666653Notes

Reaction equation

HRID 1666653 reaction equation
[Cl:1][C:2]1[N:11]=[C:10](Cl)[C:9]2[C:4](=[CH:5][CH:6]=[C:7]([O:13][CH3:14])[CH:8]=2)[N:3]=1.[CH3:15]N1CCCC1=O.C[Mg]Cl.[Cl-].[NH4+]>C1COCC1.C/C(/[O-])=C/C(C)=O.C/C(/[O-])=C/C(C)=O.C/C(/[O-])=C/C(C)=O.[Fe+3]>[Cl:1][C:2]1[N:11]=[C:10]([CH3:15])[C:9]2[C:4](=[CH:5][CH:6]=[C:7]([O:13][CH3:14])[CH:8]=2)[N:3]=1

Participants

7

Reactant 4

HCID 13387N-methyl-2-pyrrolidoneHCID 25517Ammonium ChlorideHCID 99913972,4-Dichloro-6-methoxyquinazolineHCID 178418332HCID 178418332, compound

Product 1

HCID 579701842-Chloro-6-methoxy-4-methylquinazoline

Reagents, catalysts & solvents 2

HCID 5483663Ferric acetylacetonateCatalystHCID 8028TetrahydrofuranSolvent2×

Procedure

To a mixed solution of 2,4-dichloro-6-methoxyquinazoline (CAS.105763-77-7) (0.15 g), iron(III) acetyl acetonate (0.023 g), N-methyl-2-pyrrolidinone (0.4 mL), and THF (8 mL) was added a solution (0.22 mL) of 3 M methyl magnesium chloride in THF at room temperature, and the mixture was stirred for 12 h. The reaction mixture was added dropwise to a mixture of ice (30 g) and ammonium chloride (0.3 g), and then the aqueous layer was extracted with chloroform. The organic layer was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (silica gel, chloroform) and crystallized with diisopropyl ether to obtain 2-chloro-6-methoxy-4-methylquinazoline (0.08 g).

Workup

  1. extractionthe aqueous layer was extracted with chloroform
  2. concentrationThe organic layer was concentrated under reduced pressure
  3. customthe residue was purified by silica gel column chromatography (silica gel, chloroform)
  4. customcrystallized with diisopropyl ether

Sources & evidence

ORD record
ord-c3823bd771b54c7b9bdaaff9c8c25b50
Source dataset
uspto-grants-2011_10
Patent number
US08044068B2

Reaction notes

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