Acetic Acid → Benzenemethanamine, N-butyl-2-fluoro-4-(trifluoromethyl)-

HRID 1725213Notes

Reaction equation

HRID 1725213 reaction equation
[F:1][C:2]1[CH:9]=[C:8]([C:10]([F:13])([F:12])[F:11])[CH:7]=[CH:6][C:3]=1[CH:4]=O.[CH2:14]([NH2:18])[CH2:15][CH2:16][CH3:17].C(O)(=O)C.C([BH3-])#N.[Na+]>CO.O>[CH2:14]([NH:18][CH2:4][C:3]1[CH:6]=[CH:7][C:8]([C:10]([F:13])([F:12])[F:11])=[CH:9][C:2]=1[F:1])[CH2:15][CH2:16][CH3:17]

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 8007ButylamineHCID 5229292-Fluoro-4-(trifluoromethyl)benzaldehydeHCID 5003444Sodium cyanoborohydride

Product 1

HCID 68855369Benzenemethanamine, N-butyl-2-fluoro-4-(trifluoromethyl)-Yield 26%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent

Procedure

To a solution of 2-fluoro-4-(trifluoromethyl)benzaldehyde (3.84 g, 20.0 mmol) and n-butylamine (1.46 g, 20.0 mmol) in methanol (100 mL) were added acetic acid (4.6 mL, 80 mmol) and sodium cyanoborohydride (1.51 g, 24.0 mmol) and the solution was stirred at room temperature for 3 days. Water (10 mL) was added and the mixture was concentrated in vacuo. The residue was taken up in aqueous 1 M KOH (125 mL) and ethyl acetate (100 mL) and the phases were separated. The aqueous phase was extracted with ethyl acetate (2×100 mL) and the combined organic phase was dried over Na2SO4 and concentrated in vacuo. Purification on a prepacked column of silica gel (Isolute® SPE Column, 70 g/150 mL) with ethyl acetate (33-100% gradient) in heptane as the eluent and collection of pure fractions yielded 1.28 g (26%) of a colourless oil of low viscosity.

Workup

  1. concentrationthe mixture was concentrated in vacuo
  2. customthe phases were separated
  3. extractionThe aqueous phase was extracted with ethyl acetate (2×100 mL)
  4. dry with materialthe combined organic phase was dried over Na2SO4
  5. concentrationconcentrated in vacuo
  6. customPurification on a prepacked column of silica gel (Isolute® SPE Column, 70 g/150 mL) with ethyl acetate (33-100% gradient) in heptane
  7. customas the eluent and collection of pure fractions

Sources & evidence

ORD record
ord-d4272ae34dbb43f9aafb010a0c0e4fa4
Source dataset
uspto-grants-2009_02
Patent number
US07488844B2

Reaction notes

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