Sodium Chloride → t-Butyl [3-(2-chloro-6,7-dimethoxyquinazolin-4-yl)phenyl]carbamate

HRID 453662Notes

Reaction equation

HRID 453662 reaction equation
[Cl:1][C:2]1[N:11]=[C:10](Cl)[C:9]2[C:4](=[CH:5][C:6]([O:15][CH3:16])=[C:7]([O:13][CH3:14])[CH:8]=2)[N:3]=1.B([O-])([O-])O[C:19]1[CH:24]=[CH:23][CH:22]=[C:21]([NH:25][C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])[CH:20]=1.C(=O)([O-])[O-].[Na+].[Na+].[Cl-].[Na+]>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2].C(OCC)(=O)C.O1CCCC1>[Cl:1][C:2]1[N:11]=[C:10]([C:19]2[CH:20]=[C:21]([NH:25][C:26](=[O:27])[O:28][C:29]([CH3:31])([CH3:30])[CH3:32])[CH:22]=[CH:23][CH:24]=2)[C:9]2[C:4](=[CH:5][C:6]([O:15][CH3:16])=[C:7]([O:13][CH3:14])[CH:8]=2)[N:3]=1

Participants

9

Reactant 4

HCID 5234Sodium ChlorideHCID 10340Sodium CarbonateHCID 5203272,4-Dichloro-6,7-dimethoxyquinazolineHCID 866503163-(N-t-butoxycarbonylamino)phenyl borate

Product 1

HCID 86650315t-Butyl [3-(2-chloro-6,7-dimethoxyquinazolin-4-yl)phenyl]carbamateYield 92.2%

Reagents, catalysts & solvents 4

HCID 167845palladium(II) acetateCatalystHCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)CatalystHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
60 °C

Procedure

To a mixture of 1.00 g (3.86 mmol) of 2,4-dichloro-6,7-dimethoxyquinazoline, 1.14 g (4.63 mmol) of 3-(N-t-butoxycarbonylamino)phenyl borate, tetrahydrofuran (25 mL), and 2 M sodium carbonate aqueous solution (5 mL) were added palladium acetate (8.84 mg) and 1,1′-bis(diphenylphosphino)ferrocene (21.4 mg) in this order, and the mixture was stirred at 60° C. for 6.5 hours under a nitrogen atmosphere. The reaction mixture was allowed to cool, and ethyl acetate (25 mL) and 5% w/w sodium chloride solution (20 mL) were added to extract the organic layer. The organic layer was washed twice with 5% w/w sodium chloride solution (20 mL) and then concentrated under reduced pressure. To the concentration residue were added ethyl acetate (1 mL) and 2-propanol (4 mL), and the mixture was suspended by stirring at 40° C. for 0.5 hours. The suspension was cooled, and the precipitated crystals were collected by filtration and dried to give 1.48 g of a target product (yield: 91.5%).

Workup

  1. temperatureto cool
  2. extractionto extract the organic layer
  3. washThe organic layer was washed twice with 5% w/w sodium chloride solution (20 mL)
  4. concentrationconcentrated under reduced pressure
  5. additionTo the concentration residue were added ethyl acetate (1 mL) and 2-propanol (4 mL)
  6. stirringby stirring at 40° C. for 0.5 hours
  7. temperatureThe suspension was cooled
  8. filtrationthe precipitated crystals were collected by filtration
  9. customdried

Sources & evidence

ORD record
ord-7925b615ea2440c4be9c367419c6a7f8
Source dataset
uspto-grants-2013_07
Patent number
US08492543B2

Reaction notes

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