Stannous chloride dihydrate → 3-(4-Bromo-1-methyl-1H-pyrazol-5-yl)-4-methoxyaniline

HRID 407368

Reaction equation

HRID 407368 reaction equation
[Br:1][C:2]1[CH:3]=[N:4][N:5]([CH3:18])[C:6]=1[C:7]1[CH:12]=[C:11]([N+:13]([O-])=O)[CH:10]=[CH:9][C:8]=1[O:16][CH3:17].O.O.Cl[Sn]Cl.CCOC(C)=O.CCCCCC>CCO>[Br:1][C:2]1[CH:3]=[N:4][N:5]([CH3:18])[C:6]=1[C:7]1[CH:12]=[C:11]([NH2:13])[CH:10]=[CH:9][C:8]=1[O:16][CH3:17]

Participants

5

Reactant 3

HCID 61436Stannous chloride dihydrateHCID 21226206Ethyl acetate hexaneHCID 231395414-bromo-5-(2-methoxy-5-nitrophenyl)-1-methyl-1H-pyrazole

Product 1

HCID 115727413-(4-Bromo-1-methyl-1H-pyrazol-5-yl)-4-methoxyanilineYield 88%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

To a stirred solution of 4-bromo-5-(2-methoxy-5-nitro-phenyl)-1-methyl-1H-pyrazole (1.799 g, 5.76 mmol) in EtOH (20 mL) was added SnCl2.2H2O (5.306 g, 23.05 mmol, 4.0 eq.), the mixture was stirred at reflux for 2 hrs and EtOH was removed under vacuum. The resulting solid was dissolved in EtOAc, 1N NaOH (30 mL) was added, and the mixture was stirred overnight. The white precipitate was filtered off through celite, and the aqueous phase was extracted with EtOAc (3×80 mL). The combined organic phase was dried over anhydrous MgSO4, filtered and evaporated. The crude reaction mixture was purified by SiO2 column chromatography (Eluent: EtOAc/Hexane=1/3 then 1/1) to give 3-(4-bromo-2-methyl-2H-pyrazol-3-yl)-4-methoxy-phenylamine (1.430 g, 5.07 mmol, 88%) as a white solid: LCMS m/z (%)=282 (M+H79Br, 98), 284 (M+H81Br, 100). 1H NMR (400 MHz, CDCl3 (s, 1H), 6.86 (d, J=8.8 Hz, 1H), 6.80 (dd, J=2.8, 8.8 Hz, 1H), 6.22 (d, J=2.4 Hz, 1H), 4.25 (broad s, 2H), 3.72 (s, 3H), 3.71 (s, 3H).

Workup

  1. temperatureat reflux for 2 hrs
  2. customEtOH was removed under vacuum
  3. dissolutionThe resulting solid was dissolved in EtOAc
  4. addition1N NaOH (30 mL) was added
  5. stirringthe mixture was stirred overnight
  6. filtrationThe white precipitate was filtered off through celite
  7. extractionthe aqueous phase was extracted with EtOAc (3×80 mL)
  8. dry with materialThe combined organic phase was dried over anhydrous MgSO4
  9. filtrationfiltered
  10. customevaporated
  11. customThe crude reaction mixture
  12. customwas purified by SiO2 column chromatography (Eluent

Sources & evidence

ORD record
ord-7e3b2c91dc9e4451bf5df881a1cfeb1c
Source dataset
uspto-grants-2014_06
Patent number
US08754238B2

Linked notes

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