Hydrogen Peroxide → HCID 15534003, compound

2-(4-bromobenzyloxy) 1-methoxyethane (preparation described in Example 11) (10 g) was added to a stirred mixture of oven dried magnesium (2.74 g) in tetrahydrofuran (20 ml) under an atmosphere of argon. A crystal of iodine was added and the mixture heated until an exothermic reaction commenced. A solution of the remaining 2-(4-bromobenzyloxy)-1-methoxyethane (13.4 g) in tetrahydrofuran (60 ml) was added dropwise to maintain the temperature of the reaction mixture at reflux. When the addition was complete the mixture was heated at reflux for a further 20 minutes, allowed to cool and added to trimethylborate (11.74 g) in tetrahydrofuran (60 ml) under argon at -10° C., dropwise over 45 minutes whilst maintaining the temperature below -5° C. After stirring for 15 minutes, chilled acetic acid (9.36 g) was added, followed by the dropwise addition of 30% hydrogen peroxide (11.77 ml) in water (11 ml) whilst maintaining the temperature below 0° C. The mixture was allowed to warm to ambient temperature over a period of 20 minutes and then washed successively with saturated ammonium sulphate containing ferrous ammonium sulphate until the aqueous layer no longer turned brown. The organic layer was dried (MgSO4) and evaporated. The residue was dissolved in ether (100 ml) and extracted into IM aqueous sodium hydroxide (50 ml×3). The aqueous extract was acidified with 2M aqueous hydrochloric acid and the mixture was extracted with ethyl acetate (3×50 ml). The ethyl acetate extracts were combined, dried (MgSO4) and evaporated. The residue was further purified by flash chromatography on silica gel using 10% ethyl acetate in toluene as eluent to give 2-(4-hydroxybenzyloxy)-1-methoxyethane (10.4 g) as a colourless oil; NMR (CDCl3): 3.4 (3H, s), 3.5-3.7 (4H, m), 4.5 (2H, s), 6.7-6.8 (2H, d), 7.1-7.3 (2H, d).

1. temperaturethe mixture heated until an exothermic reaction
2. temperatureto maintain the temperature of the reaction mixture
3. temperatureat reflux
4. additionWhen the addition
5. temperaturewas heated
6. temperatureat reflux for a further 20 minutes
7. temperatureto cool
8. temperaturewhilst maintaining the temperature below -5° C
9. additionwas added
10. temperaturewhilst maintaining the temperature below 0° C
11. washwashed successively with saturated ammonium sulphate
12. additioncontaining ferrous ammonium sulphate until the aqueous layer no longer turned brown
13. dry with materialThe organic layer was dried (MgSO4)
14. customevaporated
15. dissolutionThe residue was dissolved in ether (100 ml)
16. extractionextracted into IM aqueous sodium hydroxide (50 ml×3)
17. extractionThe aqueous extract
18. extractionthe mixture was extracted with ethyl acetate (3×50 ml)
19. dry with materialdried (MgSO4)
20. customevaporated
21. customThe residue was further purified by flash chromatography on silica gel using 10% ethyl acetate in toluene as eluent

ORD record

ord-b32915c43f3640758798fd9ccac76c64

Source dataset

uspto-grants-1999_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05919793