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

HRID 2374639Notes

Reaction equation

HRID 2374639 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-54625a7efccb40a4b4839b6826077ed8
Source dataset
uspto-grants-2008_12
Patent number
US07462644B2

Reaction notes

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