4-Methoxybenzylamine → 3,6-Dibromo-2-fluoro-N-[(4-methoxyphenyl)methyl]benzenemethanamine

HRID 389106Notes

Reaction equation

HRID 389106 reaction equation
[Br:1][C:2]1[C:3]([F:11])=[C:4]([C:7]([Br:10])=[CH:8][CH:9]=1)[CH:5]=O.[CH3:12][O:13][C:14]1[CH:19]=[CH:18][C:17]([CH2:20][NH2:21])=[CH:16][CH:15]=1>ClCCl>[Br:1][C:2]1[C:3]([F:11])=[C:4]([CH2:5][NH:21][CH2:20][C:17]2[CH:18]=[CH:19][C:14]([O:13][CH3:12])=[CH:15][CH:16]=2)[C:7]([Br:10])=[CH:8][CH:9]=1

Participants

4

Reactant 2

HCID 754524-MethoxybenzylamineHCID 162179253,6-Dibromo-2-fluorobenzaldehyde

Product 1

HCID 582435183,6-Dibromo-2-fluoro-N-[(4-methoxyphenyl)methyl]benzenemethanamine

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

3,6-dibromo-2-fluorobenzaldehyde (9.12 g) was dissolved in dichloromethane (45 ml), and 1-(4-methoxyphenyl)methanamine (4.6 ml) was added thereto, followed by stirring at room temperature for 4 hours. The solvent was evaporated under reduced pressure, toluene was further added thereto, followed by twice-repeated evaporation under reduced pressure and azotripic drying. The residue was dissolved in THF (25 ml), sodium borohydride (2.0 g) was added thereto, methanol (15 ml) was carefully added dropwise thereto, followed by stirring at room temperature overnight. Water was added thereto, the solvent was concentrated under reduced pressure, a 1M aqueous sodium hydroxide solution was added thereto to adjust pH to 8 or higher, followed by extraction with ethyl acetate, the organic layer was washed with water and saturated brine and was then dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel chromatography (hexane:ethyl acetate) to obtain, as a light yellow oily product, 1-(3,6-dibromo-2-fluorophenyl)-N-(4-methoxybenzyl)methanamine (8.03 g).

Workup

  1. customThe solvent was evaporated under reduced pressure, toluene
  2. additionwas further added
  3. customfollowed by twice-repeated evaporation under reduced pressure and azotripic drying
  4. dissolutionThe residue was dissolved in THF (25 ml)
  5. additionsodium borohydride (2.0 g) was added
  6. additionmethanol (15 ml) was carefully added dropwise
  7. stirringby stirring at room temperature overnight
  8. additionWater was added
  9. concentrationthe solvent was concentrated under reduced pressure
  10. additiona 1M aqueous sodium hydroxide solution was added
  11. extractionhigher, followed by extraction with ethyl acetate
  12. washthe organic layer was washed with water and saturated brine
  13. dry with materialwas then dried over anhydrous sodium sulfate
  14. customthe solvent was evaporated under reduced pressure
  15. customThe residue was purified by silica gel chromatography (hexane:ethyl acetate)

Sources & evidence

ORD record
ord-80fb50a670fd41b3aa4bfe2f129c7630
Source dataset
uspto-grants-2013_02
Patent number
US08377923B2

Reaction notes

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