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

HRID 2112178Notes

Reaction equation

HRID 2112178 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 80.5%

Reagents, catalysts & solvents 3

HCID 23994ZincCatalystHCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

1-Bromo-2-(2,4-difluoro-phenoxy)-4-methyl-5-nitro-benzene (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 was mechanically stirred vigorously for 16 hours. The reaction was filtered through Celite and the filter cake was washed with ethyl acetate. The filtrate was then concentrated with 1.2 L of saturated NH4OAc. When the THF/MeOH was removed, the solids were collected and washed with water. The solids were then stirred in 1 L water for 30 min, 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 reaction was 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. customWhen the 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 min
  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-c99d15ca251745648cf15f0f98d33a3a
Source dataset
uspto-grants-2009_04
Patent number
US07521447B2

Reaction notes

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