Toluene → (2-Amino-5-methoxyphenyl)(4-chlorophenyl)methanone

HRID 570166Notes

Reaction equation

HRID 570166 reaction equation
CC1O[C:6](=[O:8])[C:5]2[CH:9]=[C:10]([O:13][CH3:14])[CH:11]=[CH:12][C:4]=2[N:3]=1.C1(C)C=CC=CC=1.[Cl:22][C:23]1[CH:28]=[CH:27][C:26]([Mg]Br)=[CH:25][CH:24]=1>CCOCC>[NH2:3][C:4]1[CH:12]=[CH:11][C:10]([O:13][CH3:14])=[CH:9][C:5]=1[C:6]([C:26]1[CH:27]=[CH:28][C:23]([Cl:22])=[CH:24][CH:25]=1)=[O:8]

Participants

5

Reactant 3

HCID 1140TolueneHCID 6055556-methoxy-2-methyl-4H-benzo[d][1,3]oxazin-4-oneHCID 178478191HCID 178478191, compound

Product 1

HCID 13408099(2-Amino-5-methoxyphenyl)(4-chlorophenyl)methanone

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent

Procedure

To a solution of 2-methyl-6-(methyloxy)-4H-3,1-benzoxazin-4-one (for a preparation see Intermediate 8) (40.0 g, 0.21 mol) in a toluene (560 mL)/ether (200 mL) mixture at 0° C. was added dropwise a solution of 4-chlorophenylmagnesium bromide (170 mL, 1M in Et2O, 0.17 mol). The reaction mixture was allowed to warm to RT and stirred for 1 h before being quenched with 1N HCl. The aqueous layer was extracted with EtOAc (3×) and the combined organics were washed with brine, dried over Na2SO4, filtered and concentrated under reduced pressure. The crude compound was then dissolved in EtOH (400 mL) and 6N HCl (160 mL) was added. The reaction mixture was refluxed for 2 h before being concentrated under reduced pressure. The resulting solid was filtered and washed twice with ether before being suspended in EtOAc and neutralised with 1N NaOH. The aqueous layer was extracted with EtOAc (3×) and the combined organics were washed with brine, dried over Na2SO4, filtered and concentrated under reduced pressure. The title compound was obtained as a yellow solid (39 g, 88% yield) which was used without further purification.

Workup

  1. customat 0° C.
  2. custombefore being quenched with 1N HCl
  3. extractionThe aqueous layer was extracted with EtOAc (3×)
  4. washthe combined organics were washed with brine
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. dissolutionThe crude compound was then dissolved in EtOH (400 mL)
  9. addition6N HCl (160 mL) was added
  10. temperatureThe reaction mixture was refluxed for 2 h
  11. concentrationbefore being concentrated under reduced pressure
  12. filtrationThe resulting solid was filtered
  13. washwashed twice with ether
  14. extractionThe aqueous layer was extracted with EtOAc (3×)
  15. washthe combined organics were washed with brine
  16. dry with materialdried over Na2SO4
  17. filtrationfiltered
  18. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-a6002787a9fe43a5a85c394e459ce560
Source dataset
uspto-grants-2015_05
Patent number
US09023842B2

Reaction notes

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