2-Fluoro-4-iodoaniline → 4-Butyl-2-fluoroaniline

HRID 1793047Notes

Reaction equation

HRID 1793047 reaction equation
[Li][CH2:2][CH2:3][CH2:4][CH3:5].[F:6][C:7]1[CH:13]=[C:12](I)[CH:11]=[CH:10][C:8]=1[NH2:9]>C1COCC1.[Cl-].[Cl-].[Zn+2].C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH2:2]([C:12]1[CH:11]=[CH:10][C:8]([NH2:9])=[C:7]([F:6])[CH:13]=1)[CH2:3][CH2:4][CH3:5]

Participants

6

Reactant 2

HCID 1856942-Fluoro-4-iodoanilineHCID 178418339Butyllithium

Product 1

HCID 220256384-Butyl-2-fluoroanilineYield 30%

Reagents, catalysts & solvents 3

HCID 3007855ZincchlorideCatalystHCID 178418397HCID 178418397, compoundCatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

ZnCl2 (5.17 g, 38.0 mmol) was weighed into a flask, which was then flame dried and flushed with N2. Anhydrous THF (20 ml) was then added at 0° C., followed by 2.5 M nBuLi (15.2 ml, 38.0 mmol). The reaction mixture was stirred at 0° C. for 15 min, after which 2-fluoro-4-iodoaniline (3.00 g, 12.7 mmol) in anhydrous THF (10 ml) and Pd(PPh3)4 (0.74 g, 0.64 mmol) were added sequentially. The mixture was allowed to warm to RT and stirred for a further 6 h. The mixture was poured into ice/Et2O, the organic layer separated and the aqueous layer further extracted with Et2O. The combined organic fractions were washed with sat. NaHCO3, dried (Na2SO4) and concentrated under reduced pressure. The resulting solid was removed from the mixture by filtration and the filtrate purified by flash chromatography on silica (12.5% EtOAc/Hexane as eluant) to give the desired product (30%, 3.7 mmol). 1H NMR [400 MHz, CDCl3] δ 6.80 (dd, J=12.1, 1.8 Hz, 1 H), 6.76–6.65 (m, 2 H), 3.65 (br s, 2 H), 2.49 (t, J=7.7 Hz, 2 H), 1.57–1.49 (m, 2 H), 1.32 (sextet, J=7.3 Hz, 2 H), 0.91 (t, J=7.3 Hz, 3 H). LCMS (ACPI+) 168 (100%).

Workup

  1. temperaturewhich was then flame
  2. customdried
  3. customflushed with N2
  4. additionAnhydrous THF (20 ml) was then added at 0° C.
  5. temperatureto warm to RT
  6. stirringstirred for a further 6 h
  7. customthe organic layer separated
  8. extractionthe aqueous layer further extracted with Et2O
  9. washThe combined organic fractions were washed with sat. NaHCO3
  10. dry with materialdried (Na2SO4)
  11. concentrationconcentrated under reduced pressure
  12. customThe resulting solid was removed from the mixture by filtration
  13. customthe filtrate purified by flash chromatography on silica (12.5% EtOAc/Hexane as eluant)

Sources & evidence

ORD record
ord-a4c682bcb2c3452aabe8dcc2de953953
Source dataset
uspto-grants-2006_07
Patent number
US07078438B2

Reaction notes

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