4-(Trifluoromethyl)aniline → HCID 10656913, compound

HRID 426375Notes

Reaction equation

HRID 426375 reaction equation
[CH2:1]([Mg]Cl)[CH:2]=[CH2:3].F[C:7](F)(F)[C:8]1[CH:14]=[CH:13][C:11]([NH2:12])=[CH:10][CH:9]=1>C1COCC1>[CH2:1]([C:7]([C:8]1[CH:14]=[CH:13][C:11]([NH2:12])=[CH:10][CH:9]=1)([CH2:13][CH:11]=[CH2:10])[CH2:9][CH:8]=[CH2:7])[CH:2]=[CH2:3]

Participants

4

Reactant 2

HCID 99644-(Trifluoromethyl)anilineHCID 178418473HCID 178418473, compound

Product 1

HCID 10656913HCID 10656913, compoundYield 87%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

Following a literature procedure (Lin, S.-Y.; Hojjat, M; Strekowski, L. Synth. Commun. 1997, 27, 1975-1980) at 80-fold larger scale, a 2 M solution of allyl magnesium chloride in THF (0.400 L, 0.800 mol) was diluted with additional THF (1.00 L) and then treated dropwise with a solution of 4-(trifluoromethyl)aniline (19.9 mL, 0.160 mol) in THF (210 mL) at −50° C. under argon. After complete addition the sides of the reaction flask were rinsed with additional THF (150 mL). The resulting solution was heated at reflux. The reaction was monitored by TLC for the complete consumption of 4-(trifluoromethyl)aniline. After 3.5 h, the mixture was concentrated and then CH2Cl2 was added. The organic solution was washed with water, dried (Na2SO4), and filtered. The filtrate was concentrated and chromatographed [silica, CH2Cl2/hexanes (2:1)], affording a pale yellow solid (31.7 g, 87%): 1H NMR δ 2.36-2.43 (m, 6H), 3.48-3.66 (br, 2H), 4.94-5.06 (m, 6H), 5.50-5.64 (m, 3H), 6.62-6.70 (m, 2H), 7.06-7.12 (m, 2H); 13C NMR δ 42.1, 42.6, 115.0, 117.5, 127.6, 135.0, 135.8, 144.1; FABMS obsd 228.1757, calcd 228.1752 [(M+H)+, M=C16H21N].

Workup

  1. additionAfter complete addition the sides of the reaction flask
  2. washwere rinsed with additional THF (150 mL)
  3. temperatureThe resulting solution was heated
  4. temperatureat reflux
  5. customThe reaction was monitored by TLC for the complete consumption of 4-(trifluoromethyl)aniline
  6. concentrationthe mixture was concentrated
  7. additionCH2Cl2 was added
  8. washThe organic solution was washed with water
  9. dry with materialdried (Na2SO4)
  10. filtrationfiltered
  11. concentrationThe filtrate was concentrated
  12. customchromatographed [silica, CH2Cl2/hexanes (2:1)]

Sources & evidence

ORD record
ord-cd08299b003841999bcb906fd83c7ffa
Source dataset
uspto-grants-2012_01
Patent number
US08106393B2

Reaction notes

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