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

HRID 1043022Notes

Reaction equation

HRID 1043022 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.O.[Cl:16][C:17]1[CH:22]=[CH:21][C:20]([Mg]Br)=[CH:19][CH:18]=1>C1(C)C=CC=CC=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:20]1[CH:21]=[CH:22][C:17]([Cl:16])=[CH:18][CH:19]=1)=[O:8]

Participants

5

Reactant 3

HCID 962WaterHCID 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 22238780Ether tolueneSolvent

Procedure

To a solution of 2-methyl-6-(methyloxy)-4H-3,1-benzoxazin-4-one (for a preparation see Reference compound A) (40.0 g, 0.21 mol) in a toluene/ether (2/1) mixture (760 ml) at 0° C. was added dropwise a solution of 4-chlorophenylmagnesium bromide (170 ml, 1M in diethyl ether, 0.17 mol). The reaction mixture was allowed to warm to room temperature and stirred for 1 h before being quenched with 1N HCl (200 ml). The aqueous layer was extracted with EtOAc (3×150 ml) and the combined organics were washed with brine (100 ml), dried over Na2SO4, filtered and concentrated under reduced pressure. The crude compound was then dissolved in ethanol (400 ml) and 6N HCl (160 ml) was added. The reaction mixture was refluxed for 2 h before being concentrated to one-third in volume. The resulting solid was filtered and washed twice with ether before being suspended in EtOAc and neutralised with 1N sodium hydroxide. The aqueous layer was extracted with EtOAc (3×150 ml) and the combined organics were washed with brine (150 ml), dried over Na2SO4, filtered and concentrated under reduced pressure. The title compound was obtained as a yellow solid (39 g, 88% yield); LC/MS (Method D): m/z 262 [M+H]+, Rt 2.57 min.

Workup

  1. customat 0° C.
  2. custombefore being quenched with 1N HCl (200 ml)
  3. extractionThe aqueous layer was extracted with EtOAc (3×150 ml)
  4. washthe combined organics were washed with brine (100 ml)
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. dissolutionThe crude compound was then dissolved in ethanol (400 ml)
  9. addition6N HCl (160 ml) was added
  10. temperatureThe reaction mixture was refluxed for 2 h
  11. concentrationbefore being concentrated to one-third in volume
  12. filtrationThe resulting solid was filtered
  13. washwashed twice with ether
  14. extractionThe aqueous layer was extracted with EtOAc (3×150 ml)
  15. washthe combined organics were washed with brine (150 ml)
  16. dry with materialdried over Na2SO4
  17. filtrationfiltered
  18. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-f3654e7f0cf54616be7aca0d27d277a6
Source dataset
uspto-grants-2013_10
Patent number
US08557984B2

Reaction notes

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