Tetrahydrofuran → 2-Chloro-5-(2,3-difluoro-6-methoxybenzyloxy)-4-methoxyaniline Hydrochloride

HRID 1512971Notes

Reaction equation

HRID 1512971 reaction equation
[Cl:1][C:2]1[C:3]([N+:22]([O-])=O)=[CH:4][C:5]([O:10][CH2:11][C:12]2[C:17]([O:18][CH3:19])=[CH:16][CH:15]=[C:14]([F:20])[C:13]=2[F:21])=[C:6]([O:8][CH3:9])[CH:7]=1.O1CCCC1.[BH4-].[Na+].C(=O)([O-])O.[Na+]>[Ni](Br)Br.CO>[ClH:1].[Cl:1][C:2]1[CH:7]=[C:6]([O:8][CH3:9])[C:5]([O:10][CH2:11][C:12]2[C:17]([O:18][CH3:19])=[CH:16][CH:15]=[C:14]([F:20])[C:13]=2[F:21])=[CH:4][C:3]=1[NH2:22]

Participants

7

Reactant 4

HCID 8028TetrahydrofuranHCID 516892Sodium BicarbonateHCID 4311764Sodium borohydrideHCID 593097415-Chloro-2-(2,3-difluoro-6-methoxybenzyloxy)-4-nitroanisole

Product 1

HCID 685094222-Chloro-5-(2,3-difluoro-6-methoxybenzyloxy)-4-methoxyaniline HydrochlorideYield 182.5%

Reagents, catalysts & solvents 2

HCID 278492Nickel(II) bromideCatalystHCID 887MethanolSolvent

Procedure

To a mixture of 5-chloro-2-(2,3-difluoro-6-methoxybenzyloxy)-4-nitroanisole (7.04 g), nickel(II) bromide (0.21 g), tetrahydrofuran (100 mL) and methanol (100 mL) was added sodium borohydride (2.22 g) under ice-cooling, and the mixture was stirred under ice-cooling for 30 minutes, and then stirred at room temperature for 30 minutes. To the reaction mixture was added a saturated aqueous sodium hydrogen carbonate solution, and the resulting mixture was extracted with ethyl acetate. The extract was washed with brine twice, and dried over anhydrous magnesium sulfate. The solvent was removed under reduced pressure, and the residue was dissolved in ethyl acetate (20 mL). To the solution was added hydrochloric acid (4 mol/L ethyl acetate solution, 10 mL) in a dropwise manner under ice-cooling, and the mixture was stirred for 5 minutes. To the mixture was added diisopropyl ether (30 mL), and the mixture was stirred under ice-cooling for 30 minutes. The precipitated crystals were collected by filtration. The collected crystals were washed with diisopropyl ether, and dried under reduced pressure to give the title compound (6.54 g).

Workup

  1. temperaturecooling
  2. temperaturecooling for 30 minutes
  3. stirringstirred at room temperature for 30 minutes
  4. extractionthe resulting mixture was extracted with ethyl acetate
  5. washThe extract was washed with brine twice
  6. dry with materialdried over anhydrous magnesium sulfate
  7. customThe solvent was removed under reduced pressure
  8. dissolutionthe residue was dissolved in ethyl acetate (20 mL)
  9. additionTo the solution was added hydrochloric acid (4 mol/L ethyl acetate solution, 10 mL) in a dropwise manner under ice-
  10. temperaturecooling
  11. stirringthe mixture was stirred for 5 minutes
  12. additionTo the mixture was added diisopropyl ether (30 mL)
  13. stirringthe mixture was stirred under ice-
  14. temperaturecooling for 30 minutes
  15. filtrationThe precipitated crystals were collected by filtration
  16. washThe collected crystals were washed with diisopropyl ether
  17. customdried under reduced pressure

Sources & evidence

ORD record
ord-67a77793aab24abb86db22e5234e2c76
Source dataset
uspto-grants-2012_07
Patent number
US08217069B2

Reaction notes

Loading…