3-(4-Chloro-3-ethylphenoxy)aniline → N-[3-(4-chloro-3-ethylphenoxy)phenyl][[3-(pentafluoroethyl)phenyl] methyl]amine

HRID 2122206Notes

Reaction equation

HRID 2122206 reaction equation
[Cl:1][C:2]1[CH:15]=[CH:14][C:5]([O:6][C:7]2[CH:8]=[C:9]([CH:11]=[CH:12][CH:13]=2)[NH2:10])=[CH:4][C:3]=1[CH2:16][CH3:17].[F:18][C:19]([F:32])([C:24]1[CH:25]=[C:26]([CH:29]=[CH:30][CH:31]=1)[CH2:27]Br)[C:20]([F:23])([F:22])[F:21]>C1CCCCC1.CCOCC.C([O-])(O)=O.[Na+]>[Cl:1][C:2]1[CH:15]=[CH:14][C:5]([O:6][C:7]2[CH:8]=[C:9]([NH:10][CH2:27][C:26]3[CH:29]=[CH:30][CH:31]=[C:24]([C:19]([F:18])([F:32])[C:20]([F:21])([F:23])[F:22])[CH:25]=3)[CH:11]=[CH:12][CH:13]=2)=[CH:4][C:3]=1[CH2:16][CH3:17]

Participants

6

Reactant 2

HCID 110212303-(4-Chloro-3-ethylphenoxy)anilineHCID 232370621-(Bromomethyl)-3-(pentafluoroethyl)benzene

Product 1

HCID 10994113N-[3-(4-chloro-3-ethylphenoxy)phenyl][[3-(pentafluoroethyl)phenyl] methyl]amineYield 35.1%

Reagents, catalysts & solvents 3

HCID 3283Diethyl EtherSolventHCID 8078CyclohexaneSolvent2×HCID 516892Sodium BicarbonateSolvent

Procedure

EX-66° C.) A solution of 3-(4chloro-3-ethylphenoxy)aniline (1.7 g, 6.9 mmol) was prepared in cyclohexane (13 mL). A solution of crude 3-pentafluoroethyl benzylbromide (1 g, 3.5 mmol) product from EX-660B in cyclohexane (10 mL) was added dropwise over 3 min. The reaction mixture was refluxed under N2 for 24 h and then was cooled to room temperature. The mixture was diluted with Et2O and saturated aqueous NaHCO3. The layers were separated, and the aqueous layer was extracted with Et20. The organic layer was washed with brine, dried with anhydrous MgSO4, filtered and concentrated in vacuo. The residue was purified by chromatography on silica gel eluting with hexanes in ethyl acetate (95:5) which gave 0.56 g (35%) of the desired N-[3-(4-chloro-3-ethylphenoxy)phenyl][[3-(pentafluoroethyl)phenyl] methyl]amine product as an amber oil. 1H NMR (CDCl3) δ 7.53 (m, 4H), 7.27 (d, 1H), 7.15 (t, 1H), 6.93 (d, 1H), 6.77 (dd, 1H), 6.41 (tt, 2H), 6.30 (t, 1H), 4.41 (s, 2H), 2.73 (q, 2H), 1.23 (t, 3H). 13C NMR (CDCl3) δ 158.6, 156.1, 143.4, 141.3, 140.2, 131.3, 130.7, 130.4, 129.4, 128.1, 120.4, 117.8, 108.8. 103.9, 48.5, 27.5, 14.1. 19F NMR (CDCl3) δ −85.1 (s, 3F), −115.2 (s, 2F). HRMS calcd. for C23H19CIF5NO: 456.1154 [M+H]+, found: 456.1164.

Workup

  1. custom66° C.
  2. temperatureThe reaction mixture was refluxed under N2 for 24 h
  3. customThe layers were separated
  4. extractionthe aqueous layer was extracted with Et20
  5. washThe organic layer was washed with brine
  6. dry with materialdried with anhydrous MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe residue was purified by chromatography on silica gel eluting with hexanes in ethyl acetate (95:5) which

Sources & evidence

ORD record
ord-69a0b6801ed74311b7c906003803e04f
Source dataset
uspto-grants-2004_02
Patent number
US06696472B2

Reaction notes

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