Ammonium Chloride → 5-Bromo-4-(2,4-difluorophenoxy)-2-methylbenzenamine

HRID 912444Notes

Reaction equation

HRID 912444 reaction equation
[Br:1][C:2]1[CH:7]=[C:6]([N+:8]([O-])=O)[C:5]([CH3:11])=[CH:4][C:3]=1[O:12][C:13]1[CH:18]=[CH:17][C:16]([F:19])=[CH:15][C:14]=1[F:20].[NH4+].[Cl-]>C1COCC1.CO.[Zn]>[Br:1][C:2]1[C:3]([O:12][C:13]2[CH:18]=[CH:17][C:16]([F:19])=[CH:15][C:14]=2[F:20])=[CH:4][C:5]([CH3:11])=[C:6]([NH2:8])[CH:7]=1

Participants

6

Reactant 2

HCID 25517Ammonium ChlorideHCID 574187591-Bromo-2-(2,4-difluorophenoxy)-4-methyl-5-nitrobenzene

Product 1

HCID 574187605-Bromo-4-(2,4-difluorophenoxy)-2-methylbenzenamineYield 81%

Reagents, catalysts & solvents 3

HCID 23994ZincCatalystHCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

1-Bromo-2-(2,4-difluorophenoxy)-4-methyl-5-nitrobenzene (87.0 g, 253 mmol) was dissolved in THF (300 mL) and diluted with MeOH (900 mL). Zinc dust (82.7 g, 1.26 mol) was added and 1 L of saturated NH4Cl was added slowly so that the reaction temperature never exceeded 42° C. The reaction mixture was mechanically stirred vigorously for 16 hours, and the filtered through Celite and the filter cake was washed with ethyl acetate. The filtrate was then concentrated with 1.2 L of saturated NH4OAc. The THF/MeOH was removed and the solids were collected and washed with water. The solids were then stirred in 1 L water for 30 minutes, then collected via filtration and rinsed with water (1 L) in three portions. The resulting solid was dried under high vacuum for 48 hours to produce 64 g of the desired product (81% yield). MS (ESI+) m/z 314,316 (M+1, Br pattern) detected; 1H NMR (400 MHz, CDCl3) δ 6.92 (m, 1H), 6.91 (s, 1H), 6.75 (m, 2H), 6.70 (s, 1H), 3.57 (br. s, 2H), 2.08 (s, 3H).

Workup

  1. filtrationthe filtered through Celite
  2. washthe filter cake was washed with ethyl acetate
  3. concentrationThe filtrate was then concentrated with 1.2 L of saturated NH4OAc
  4. customThe THF/MeOH was removed
  5. customthe solids were collected
  6. washwashed with water
  7. stirringThe solids were then stirred in 1 L water for 30 minutes
  8. filtrationcollected via filtration
  9. washrinsed with water (1 L) in three portions
  10. customThe resulting solid was dried under high vacuum for 48 hours

Sources & evidence

ORD record
ord-790e05a6b5ba4bae9485e712d88d4423
Source dataset
uspto-grants-2011_09
Patent number
US08026233B2

Reaction notes

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