Hydrochloric Acid → 4-[4-(Benzyloxy)phenoxy]aniline

HRID 392394Notes

Reaction equation

HRID 392394 reaction equation
[CH2:1]([O:8][C:9]1[CH:24]=[CH:23][C:12]([O:13][C:14]2[CH:19]=[CH:18][C:17]([N+:20]([O-])=O)=[CH:16][CH:15]=2)=[CH:11][CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Cl>C(O)C.[Fe]>[CH2:1]([O:8][C:9]1[CH:24]=[CH:23][C:12]([O:13][C:14]2[CH:15]=[CH:16][C:17]([NH2:20])=[CH:18][CH:19]=2)=[CH:11][CH:10]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

5

Reactant 2

HCID 313Hydrochloric AcidHCID 2799699HCID 2799699, compound

Product 1

HCID 226636594-[4-(Benzyloxy)phenoxy]anilineYield 76%

Reagents, catalysts & solvents 2

HCID 23925IronCatalyst2×HCID 702EthanolSolvent

Conditions

Temperature
57.5 °C

Procedure

A mechanically-stirred solution of 4-(4-benzyloxyphenoxy)-1-nitrobenzene (5.6 g, 17 mmol) in absolute ethanol (50 ml) was treated with concentrated hydrochloric acid (6 ml). The solution was warmed to 55-60° C. under a nitrogen cover. Iron powder (6.5 g, 115 mmol) was added in several portions. A mild exotherm (while still being heated) brought the reaction temperature to 68° C. After completing the iron addition the reaction temperature was brought to 70° C. and maintained at that temperature for 1.5 hours. The mixture was then cooled to room temperature and filtered through a pad of Celite®. The filter cake was washed with ethanol (100 ml) and methylene chloride (50 ml), and the filtrate partitioned between methylene chloride and 1M potassium carbonate. The green aqueous layer was extracted a second time with methylene chloride and then dried over anhydrous magnesium sulfate. Filtration and concentration in vacuo afforded crude product (5.4 g), contaminated with unreacted starting material. Silica gel chromatography (Waters® LC2000 with 2 PrePak® columns, eluting with methylene chloride) provided the title compound (3.75 g, 76%), as well as unreacted starting material (1.2 g). 1H NMR(400 MHz): 3.53(2H,br s), 5.02(2H,s), 6.62-6.67(2H,m), 6.79-6.84(2H,m), 6.86-6.93(4H,m), 7.29-7.44(5H,m); MS(ESI)m/z 291.9([M+H]+,100).

Workup

  1. temperatureA mild exotherm (while still being heated)
  2. customto 68° C
  3. customwas brought to 70° C.
  4. temperaturemaintained at that temperature for 1.5 hours
  5. temperatureThe mixture was then cooled to room temperature
  6. filtrationfiltered through a pad of Celite®
  7. washThe filter cake was washed with ethanol (100 ml) and methylene chloride (50 ml)
  8. customthe filtrate partitioned between methylene chloride and 1M potassium carbonate
  9. extractionThe green aqueous layer was extracted a second time with methylene chloride
  10. dry with materialdried over anhydrous magnesium sulfate
  11. filtrationFiltration and concentration in vacuo
  12. customafforded crude product (5.4 g)
  13. washSilica gel chromatography (Waters® LC2000 with 2 PrePak® columns, eluting with methylene chloride)

Sources & evidence

ORD record
ord-0df2312a5ae54f02a637c0db5ab9d4ec
Source dataset
uspto-grants-2004_10
Patent number
US06800651B2

Reaction notes

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