Aniline → 4-(2-Chloro-1,1,2,2-tetrafluoroethyl)aniline

HRID 924137Notes

Reaction equation

HRID 924137 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[Cl:8][C:9]([F:15])([F:14])[C:10]([F:13])([F:12])I.C([O-])(O)=O.[Na+]>CN(C=O)C.CCOCC.C1C=CC([P]([Ni]([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>[Cl:8][C:9]([F:15])([F:14])[C:10]([C:5]1[CH:6]=[CH:7][C:2]([NH2:1])=[CH:3][CH:4]=1)([F:13])[F:12]

Participants

7

Reactant 3

HCID 6115AnilineHCID 1362681-Chloro-2-iodotetrafluoroethaneHCID 516892Sodium Bicarbonate

Product 1

HCID 867026324-(2-Chloro-1,1,2,2-tetrafluoroethyl)aniline

Reagents, catalysts & solvents 3

HCID 178420538HCID 178420538, compoundCatalystHCID 3283Diethyl EtherSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

Ni(PPh3)4 (222 mg, 0.2 mmol) was added to a mixture of aniline (745 mg, 8 mmol) and 1-chloro-1,1,2,2-tetrafluoro-2-iodoethane (1049 mg, 4 mmol) in DMF (10 mL) in a MW vial under an argon atmosphere. The vial was sealed and the RM was stirred for two days at 80° C. After cooling at RT, the RM was dissolved in Et2O, washed with NaHCO3 10% and brine, dried over MgSO4 and the solvent was evaporated off under reduce pressure to give a residue which was purified by flash chromatography (RediSep® Silica gel column, n-heptane/EtOAc, from 0 to 25% EtOAc) and further by reverse phase chromatography (MPLC, Lichroprep® 15-25 μm column, eluents: water+0.1% formic/MeCN+0.1% formic acid, gradient 10 to 50% MeCN+0.1% formic acid). The fractions containing pure product were combined and the MeCN was evaporated off under reduced pressure to give an aq. phase which was neutralized with NaHCO3 and extracted with Et2O. The combined extracts were dried over MgSO4 and the solvent was evaporated off under reduced pressure to afford the title compound as a red oil. HPLC (Condition 4) tR=5.48 min, UPLC-MS (Condition 3) tR=1.04 min, m/z=269 [M+H]+.

Workup

  1. customThe vial was sealed
  2. temperatureAfter cooling at RT
  3. washwashed with NaHCO3 10% and brine
  4. dry with materialdried over MgSO4
  5. customthe solvent was evaporated off
  6. customto give a residue which
  7. customwas purified by flash chromatography (RediSep® Silica gel column, n-heptane/EtOAc, from 0 to 25% EtOAc) and further by reverse phase chromatography (MPLC, Lichroprep® 15-25 μm column, eluents: water+0.1% formic/MeCN+0.1% formic acid, gradient 10 to 50% MeCN+0.1% formic acid)
  8. additionThe fractions containing pure product
  9. customthe MeCN was evaporated off under reduced pressure
  10. customto give an aq. phase which
  11. extractionextracted with Et2O
  12. dry with materialThe combined extracts were dried over MgSO4
  13. customthe solvent was evaporated off under reduced pressure

Sources & evidence

ORD record
ord-0f34e482105e46c78f8e26c083cfefab
Source dataset
uspto-grants-2016_03
Patent number
US09278981B2

Reaction notes

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