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

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).

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

ORD record

ord-dd371e70fd7a4cd3873e4fcabf8be294

Source dataset

uspto-grants-2011_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08039472B2