4-Aminophenol → HCID 506617, compound

HRID 392403Notes

Reaction equation

HRID 392403 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([OH:8])=[CH:4][CH:3]=1.[CH:9]1[CH:14]=[N:13][CH:12]=[C:11]([CH:15]=O)[CH:10]=1.[BH4-].[Na+]>C1C=CC=CC=1>[OH:8][C:5]1[CH:6]=[CH:7][C:2]([NH:1][CH2:15][C:11]2[CH:12]=[N:13][CH:14]=[CH:9][CH:10]=2)=[CH:3][CH:4]=1

Participants

5

Reactant 3

HCID 4034-AminophenolHCID 103713-PyridinecarboxaldehydeHCID 4311764Sodium borohydride

Product 1

HCID 506617HCID 506617, compound

Reagents, catalysts & solvents 1

HCID 241BenzeneSolvent

Conditions

Temperature
0 °C

Procedure

To a mixture of 4-aminophenol (Aldrich; 1.0 equiv.) in benzene (1 M) was added 3-pyridenecarboxaldehyde (Aldrich; 1.0 equiv.). The flask was fitted with a Dean-Stark trap and heated to reflux overnight. (A solid mass formed on the bottom of the flask, which was difficult to break up). The reaction was cooled to ambient and concentrated in vacuo. The solid was taken up in methanol (0.2 M), cooled to 0° C., and treated with sodium borohydride (1.5 equiv.) in 4 portions. The cooling bath was removed and stirring continued for 2 hours. A small amount of was added to quench unreacted hydride. The reaction was concentrated in vacuo. The residue was partitioned between ethyl acetate and water. The aqueous layer was back-extracted with ethyl acetate. The combined organics were washed with brine, dried over sodium sulfate, filtered, and concentrated. The crude solid was recrystallized from hexanes/ethyl acetate to give N-(4-hydroxyphenyl)pyridin-3-ylmethylamine. 1H NMR (400 MHz, DMSO d6) 4.16 (2H, s), 6.41 (2H, m), 6.48 (2H, m), 7.28 (1H, ddd, J=0.73, 4.8, 7.7 Hz), 7.7 (1H, td, J=2.2, 7.3 Hz), 8.38 (1H, m), 8.39 (1H, s), 8.52 (1H, d, J=1.5 Hz).

Workup

  1. customThe flask was fitted with a Dean-Stark trap
  2. temperatureheated
  3. temperatureto reflux overnight
  4. custom(A solid mass formed on the bottom of the flask, which
  5. temperatureThe reaction was cooled to ambient and
  6. concentrationconcentrated in vacuo
  7. customThe cooling bath was removed
  8. additionA small amount of was added
  9. customto quench unreacted hydride
  10. concentrationThe reaction was concentrated in vacuo
  11. customThe residue was partitioned between ethyl acetate and water
  12. extractionThe aqueous layer was back-extracted with ethyl acetate
  13. washThe combined organics were washed with brine
  14. dry with materialdried over sodium sulfate
  15. filtrationfiltered
  16. concentrationconcentrated
  17. customThe crude solid was recrystallized from hexanes/ethyl acetate

Sources & evidence

ORD record
ord-b637c3cba50f4c08b94dd7f77c9392c0
Source dataset
uspto-grants-2004_10
Patent number
US06800651B2

Reaction notes

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