4-(4-Hydroxyphenyl)butanoic acid → 4-(4-Hydroxybutyl)phenol

HRID 2365490Notes

Reaction equation

HRID 2365490 reaction equation
[OH:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][CH2:9][CH2:10][C:11](O)=[O:12])=[CH:4][CH:3]=1.CSC.B>C1COCC1>[OH:12][CH2:11][CH2:10][CH2:9][CH2:8][C:5]1[CH:4]=[CH:3][C:2]([OH:1])=[CH:7][CH:6]=1

Participants

4

Reactant 2

HCID 2799834-(4-Hydroxyphenyl)butanoic acidHCID 12423031(Dimethyl sulfide)trihydroboron

Product 1

HCID 133925134-(4-Hydroxybutyl)phenol

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

4-(4-Hydroxy-phenyl)-butyric acid (22.1 g, 123 mmol) is dissolved in THF (750 ml) and borane-dimethyl sulfide (23.3 ml, 245 mmol) is slowly added. The yellow suspension formed is heated at reflux for 3 hours until most of the solid slowly dissolves. The flask is removed from the heating mantle, and MeOH is slowly added until bubbling ceases and the residual solid has dissolved. The flask is cooled to room temperature and water (1 L) is added. The pH is corrected to 3 with AcOH, then the mixture is extracted with EtOAc (2×500 ml). The organics are washed with brine, dried (MgSO4) and concentrated. The crude product is slurried with silica (500 g) in 25% EtOAc/iso-hexanes (1 L). This is filtered, then flushed with 50% EtOAc/iso-hexanes (2 L) to elute the product. The organics are concentrated to give 4-(4-Hydroxy-butyl)-phenol as a brown oil which crystallizes on standing; 1H NMR (CDCl3): 1.55-1.72 (4H, m), 2.58 (2H, t, J=7.0 Hz), 3.1 (2H, br signal), 3.70 (2H, t, J=6.4 Hz), 6.77 (2H, d, J=8.4 Hz), 7.05 (2H, d, J=8.4 Hz).

Workup

  1. customThe yellow suspension formed
  2. temperatureis heated
  3. temperatureat reflux for 3 hours until most of the solid
  4. dissolutionslowly dissolves
  5. customThe flask is removed from the heating mantle, and MeOH
  6. additionis slowly added
  7. customuntil bubbling ceases
  8. dissolutionthe residual solid has dissolved
  9. additionwater (1 L) is added
  10. extractionthe mixture is extracted with EtOAc (2×500 ml)
  11. washThe organics are washed with brine
  12. dry with materialdried (MgSO4)
  13. concentrationconcentrated
  14. filtrationThis is filtered
  15. customflushed with 50% EtOAc/iso-hexanes (2 L)
  16. washto elute the product
  17. concentrationThe organics are concentrated

Sources & evidence

ORD record
ord-9760fa9879024ae6b586b3d317858ddd
Source dataset
uspto-grants-2014_04
Patent number
US08697687B2

Reaction notes

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