Benzaldehyde → N-benzyl-2-fluoro-5-methoxyaniline

HRID 567359Notes

Reaction equation

HRID 567359 reaction equation
[F:1][C:2]1[CH:8]=[CH:7][C:6]([O:9][CH3:10])=[CH:5][C:3]=1[NH2:4].[CH:11](=O)[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1.C([BH3-])#N.[Na+]>CO.[Cl-].[Zn+2].[Cl-]>[CH2:11]([NH:4][C:3]1[CH:5]=[C:6]([O:9][CH3:10])[CH:7]=[CH:8][C:2]=1[F:1])[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1

Participants

6

Reactant 3

HCID 240BenzaldehydeHCID 5003444Sodium cyanoborohydrideHCID 135590752-Fluoro-5-methoxyaniline

Product 1

HCID 22741334N-benzyl-2-fluoro-5-methoxyanilineYield 90%

Reagents, catalysts & solvents 2

HCID 3007855ZincchlorideCatalystHCID 887MethanolSolvent

Procedure

This procedure was patterned after that of Tietze and Grote, Chem Ber. 126(12), 2733 (1993). A solution of 2.73 g of 2-fluoro-5-methoxyaniline and 2.67 g of benzaldehyde in 48 ml of methanol was treated with 3.43 g of zinc chloride and then cooled in an ice bath. Sodium cyanoborohydride (1.58 g) was added in small poroom temperature ions over 30 minutes and the reaction was stirred for five hours at room temperature. After evaporation of the solvent, the residue was slurried in 40 ml of 1 N sodium hydroxide solution and then extracted twice with ether. The extracts were washed with water and then with brine, dried over magnesium sulfate and concentrated. The residue was recrystallized from hexane to afford 2.61 g and the mother liquors were chromatographed on silica gel using 20:1 hexane/ether to afford another 1.4 g of the subtitle compound (90%). mp. 56-58° C.

Workup

  1. temperaturecooled in an ice bath
  2. customAfter evaporation of the solvent
  3. extractionextracted twice with ether
  4. washThe extracts were washed with water
  5. dry with materialwith brine, dried over magnesium sulfate
  6. concentrationconcentrated
  7. customThe residue was recrystallized from hexane
  8. customto afford 2.61 g
  9. customthe mother liquors were chromatographed on silica gel using 20:1 hexane/ether

Sources & evidence

ORD record
ord-fbf7d6d9c1db4857ae8e900fb9392863
Source dataset
uspto-grants-2001_01
Patent number
US06177440B1

Reaction notes

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