Reaction #1833283

Reaction equation

sodium hydroxide

5-chloro-2-(hydroxymethyl)phenol

benzyl bromide

→

solid

{4-Chloro-2-[(phenylmethyl)oxy]phenyl}methanol

Solvents

ethanol

ethanol

water

dichloromethane

Conditions

Workup

1. 1
   OtherThe solvent was removed in vacuo
2. 2
   Otherto leave an aqueous suspension
3. 3
   OtherThe phases were separated
4. 4
   Extractionthe aqueous phase extracted with dichloromethane (30 ml)
5. 5
   WashThe combined organic extracts were washed with saturated aqueous sodium hydrogen carbonate (20 ml)
6. 6
   Otherthe solvent removed in vacuo

Procedure

To a solution of 5-chloro-2-(hydroxymethyl)phenol (for a preparation see intermediate 5; 1.51 g, 9.54 mmol) in ethanol (20 ml), was added sodium hydroxide (5.25 ml, 10.5 mmol). To the mixture was added a solution of benzyl bromide (Aldrich; 1.14 ml, 9.54 mmol) in ethanol (30 ml) dropwise. The reaction was stirred under nitrogen overnight at ambient temperature. The solvent was removed in vacuo to leave an aqueous suspension. The suspension was diluted with water (50 ml) and dichloromethane (40 ml). The phases were separated and the aqueous phase extracted with dichloromethane (30 ml). The combined organic extracts were washed with saturated aqueous sodium hydrogen carbonate (20 ml) and the solvent removed in vacuo to leave a white solid (1.52 g). The residue was loaded in dichloromethane and purified on silica (100 g) using 0-50% ethyl acetate-cyclohexane. The appropriate fractions were combined and evaporated in vacuo to give the title compound (1.32 g) as a white solid; LCMS (System 2): (M-H)−=247, tRET=1.17 min.

Source