Reaction #1833281

Reaction equation

2-(hydroxymethyl)phenol

1-bromobutane

NaOH

→

title compound

Yield 77.7%

[2-(Butyloxy)phenyl]methanol

Yield 77.7%

Solvents

ethanol

water

Conditions

Workup

1. 1
   Othergiving a reaction time of 30 minutes
2. 2
   OtherAfter all starting solutions had been consumed
3. 3
   Otherthe system was purged with an additional 70 ml solvent (1:1, ethanol:water)
4. 4
   ConcentrationThe collected material was concentrated in vacuo
5. 5
   OtherThe residue was partitioned between water and EtOAc
6. 6
   workup.ADDITIONtreated with saturated aqueous sodium bicarbonate solution
7. 7
   ExtractionThe aqueous phase was further extracted with EtOAc
8. 8
   Otherthe combined organic extracts were dried (hydrophobic frit)
9. 9
   Concentrationconcentrated in vacuo
10. 10
    OtherThe residue was purified on silica (100 g)
11. 11
    Concentrationconcentrated in vacuo

Procedure

A solution of 2-(hydroxymethyl)phenol (Aldrich; 1.24 g, 10 mmol) and 1-bromobutane (Acros; 1.18 ml, 11 mmol) in ethanol (5 ml) (total volume approximately 7 ml) was mixed in a flow reactor (Vapourtec R4, 30 ml PFA tubing, 110° C.) with a solution of aqueous NaOH (2 N, 5 ml, 10 mmol) in water (2 ml). The reagents were each pumped at 0.5 ml/min), giving a reaction time of 30 minutes. After the 30 ml reactor, the solution passed through a second “cooling” reactor (5 ml) at 50° C. At the reactor output, a 250 psi back pressure regulator was used. After all starting solutions had been consumed, the system was purged with an additional 70 ml solvent (1:1, ethanol:water). The collected material was concentrated in vacuo. The residue was partitioned between water and EtOAc, and treated with saturated aqueous sodium bicarbonate solution. The aqueous phase was further extracted with EtOAc, and the combined organic extracts were dried (hydrophobic frit) and concentrated in vacuo. The residue was purified on silica (100 g) using 0-100% ethyl acetate-cyclohexane. The appropriate fractions were combined and concentrated in vacuo to give the title compound (1.4 g); LCMS (System 4): MNH4+=198, tRET=2.51 min.

Source