Boron trifluoride etherate → 3-Fluoro-4-methoxybenzylamine

HRID 906071Notes

Reaction equation

HRID 906071 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH:8]=[CH:9][C:10]=1[O:11][CH3:12])[C:5]([NH2:7])=O.[BH4-].[Na+].B(F)(F)F.CCOCC>O1CCCC1.C(OCC)(=O)C>[F:1][C:2]1[CH:3]=[C:4]([CH:8]=[CH:9][C:10]=1[O:11][CH3:12])[CH2:5][NH2:7]

Participants

6

Reactant 3

HCID 8000Boron trifluoride etherateHCID 4311764Sodium borohydrideHCID 177507693-Fluoro-4-methoxybenzamide

Product 1

HCID 143925883-Fluoro-4-methoxybenzylamineYield 61%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 3-fluoro-4-(methyloxy)benzamide (100 mg, 0.60 mmol) in tetrahydrofuran (5 mL) was added sodium borohydride (115 mg, 3.0 mmol) followed by the drop-wise addition of a solution of borontrifluoride etherate (48% BF3 ca., 475 μl, 3.8 mmol) in tetrahydrofuran (3 mL). The mixture was stirred at reflux for 15 hours, then was cooled to room temperature and diluted with ethyl acetate. The organic portion was extracted with 20% aqueous citric acid. The aqueous portion was brought to pH 8 using solid sodium bicarbonate, then was extracted several times using ethyl acetate. The combined organic portion was washed with brine then dried over anhydrous sodium sulfate. Filtration and concentration afforded a yellow residue, which was purified by silica gel column chromatography using 10% methanol in dichloromethane as eluent. Purified fractions were pooled and concentrated to afford 56 mg, 0.36 mmol (61%) of 3-fluoro-4-methoxybenzylamine as a colorless residue. MS (EI) for C8H10FNO: 156 (MH+).

Workup

  1. temperatureat reflux for 15 hours
  2. extractionThe organic portion was extracted with 20% aqueous citric acid
  3. extractionwas extracted several times
  4. washThe combined organic portion was washed with brine
  5. dry with materialthen dried over anhydrous sodium sulfate
  6. filtrationFiltration and concentration
  7. customafforded a yellow residue, which
  8. customwas purified by silica gel column chromatography
  9. concentrationconcentrated

Sources & evidence

ORD record
ord-c9a4b2ddc1f94baa94cc3fddcf76ccca
Source dataset
uspto-grants-2011_09
Patent number
US08012956B2

Reaction notes

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