1,3-Dibromo-5,5-dimethylhydantoin → 1-Bromo-3-(bromomethyl)-5-methoxybenzene

Temperatur

80 °C

5,5-Dimethyl-1,3-dibromohydantoin (13.1 g, 46 mmol) and azobisisobutyronitrile (1.50 g, 9.1 mmol) were simultaneously added at 80° C. to a solution of 1-bromo-3-methoxy-5-methylbenzene (17.0 g, 91 mmol) synthesized by a method of the document (J. Med. Chem. 2001, 44, 1866) in monochlorobenzene (500 mL), and the reaction mixture was stirred at 80° C. for 30 minutes. The reaction solution was cooled to room temperature and then poured into a 10% aqueous sodium thiosulfate solution (100 mL), and the mixture was stirred for 30 minutes. The mixture was separated into aqueous and organic layers. The aqueous layer was subjected to extraction with toluene (100 mL). The combined organic layers were dried over anhydrous sodium sulfate, and the solvent was then distilled off under reduced pressure to obtain 1-bromo-3-(bromomethyl)-5-methoxybenzene. Without further purification, this compound was dissolved in triethyl phosphite (14.3 mL, 97 mmol) and toluene (50 mL), and the reaction mixture was heated under reflux for 7 hours. After cooling to room temperature, the solvent was distilled off under reduced pressure. The obtained concentrated residue was purified by silica gel column chromatography (n-hexane:ethyl acetate=1:2) to obtain the title compound (1-2-1) (20.8 g, 64%).

1. temperatureThe reaction solution was cooled to room temperature
2. stirringthe mixture was stirred for 30 minutes
3. customThe mixture was separated into aqueous and organic layers
4. extractionThe aqueous layer was subjected to extraction with toluene (100 mL)
5. dry with materialThe combined organic layers were dried over anhydrous sodium sulfate
6. distillationthe solvent was then distilled off under reduced pressure

ORD-Eintrag

ord-9f692c1bd73f4405b73e62d7ae35be75

Quelldatensatz

uspto-grants-2011_11

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08063223B2