Phosphorus tribromide → HCID 66770954, compound

To a solution of 4-chloro-3-(hydroxymethyl)phenol (for as preparation see Intermediate 12) (3.3 g, 20.8 mmol) in ethanol (30 ml) was added 2 M sodium hydroxide (10 ml, 20 mmol). To the mixture was added dropwise a solution of benzyl bromide (2.48 ml, 20.8 mmol, Aldrich) in ethanol (30 ml). The reaction was stirred under nitrogen overnight at ambient temperature. The ethanol was removed in vacuo to leave a cream solid and the residue partitioned between water (80 ml) and dichloromethane (60 ml). The phases were separated and the aqueous phase extracted with dichloromethane (40 ml). The combined organic extracts were washed with saturated aqueous sodium hydrogen carbonate (40 ml) and the solvent removed in vacuo to leave a white solid (4.6 g). The sample was loaded in dichloromethane and purified on silica (2×100 g) using 0-100% ethyl acetate-cyclohexane. The appropriate fractions were combined and evaporated in vacuo to give {2-chloro-5-[(phenylmethyl)oxy]phenyl}methanol as a clear oil (4.12 g). To a solution of {2-chloro-5-[(phenylmethyl)oxy]phenyl}methanol (1.22 g, 4.91 mmol) in DCM (25 ml) at −10 to −15° C., under nitrogen, was added a solution of phosphorus tribromide (0.463 ml, 4.91 mmol, Aldrich) in DCM (10 ml) dropwise. The solution was allowed to warm to ambient temperature and stirred for 3 h under nitrogen. To the reaction mixture in an ice-bath was added dropwise saturated aqueous sodium hydrogen carbonate (15 ml). The mixture was diluted with water (80 ml) and DCM (100 ml). The phases were separated and the aqueous phase washed with DCM (60 ml). The combined organic extracts were washed with water (50 ml). The organic extract was dried (MgSO4), filtered and the solvent removed in vacuo to give 3-(bromomethyl)-4-chlorophenyl phenylmethyl ether as a colourless gum (1.11 g).

1. customThe phases were separated
2. washthe aqueous phase washed with DCM (60 ml)
3. washThe combined organic extracts were washed with water (50 ml)
4. extractionThe organic extract
5. dry with materialwas dried (MgSO4)
6. filtrationfiltered
7. customthe solvent removed in vacuo

ORD record

ord-fcaaf8e53ca747ec8dc27a52655c77d4

Source dataset

uspto-grants-2013_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08399436B2