Benzyl Chloride → 3-Benzyloxy-4-fluoro-phenylamine

HRID 2415498Notes

Reaction equation

HRID 2415498 reaction equation
[F:1][C:2]1[CH:8]=[CH:7][C:5]([NH2:6])=[CH:4][C:3]=1[OH:9].[CH2:10](Cl)[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1>CN(C=O)C>[CH2:10]([O:9][C:3]1[CH:4]=[C:5]([NH2:6])[CH:7]=[CH:8][C:2]=1[F:1])[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1

Participants

4

Reactant 2

HCID 7503Benzyl ChlorideHCID 226414135-Amino-2-fluorophenol

Product 1

HCID 226414853-Benzyloxy-4-fluoro-phenylamineYield 68.8%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

79 g (0.62 mol) of 4-fluoro-3-hydroxy-aniline in DMF (1.3 l) were treated under argon portion wise over a period of 15 minutes with 76.7 g (0.68 mol) of potassium t-butylate whereas the temperature of the reaction solution was kept between RT and 28° C. Stirring was continued for 15 minutes then 79 ml (0.68 mol) of benzyl chloride were added dropwise while keeping the temperature of the reaction solution between RT and 30° C. After stirring for 2 h at RT the reaction solution was poured into ice water (6 l) which was then extracted 3-fold with ether (about 3 l each). The combined organic layers were washed with brine (1.5 l) and dried over magnesium sulfate and the solvent removed in vacuo. The residue was purified by chromatography over a short silica gel column with methylene chloride as eluent. Combination of the purified fractions and concentration in vacuo gave 92.7 g (68.6%) of the desired 3-benzyloxy-4-fluoro-phenylamine as light yellow crystalline solid. ISP mass spectrum, m/e: 218.2 (M+1 calculated for C13H12FNO: 218.2).

Workup

  1. customwas kept between RT and 28° C
  2. customthe temperature of the reaction solution between RT and 30° C
  3. stirringAfter stirring for 2 h at RT the reaction solution
  4. extractionwas then extracted 3-fold with ether (about 3 l each)
  5. washThe combined organic layers were washed with brine (1.5 l)
  6. dry with materialdried over magnesium sulfate
  7. customthe solvent removed in vacuo
  8. customThe residue was purified by chromatography over a short silica gel column with methylene chloride as eluent
  9. concentrationCombination of the purified fractions and concentration in vacuo

Sources & evidence

ORD record
ord-c0e06501f6ce48c383deb3cc75a20643
Source dataset
uspto-grants-2004_11
Patent number
US06818767B2

Reaction notes

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