Methyl iodide → HCID 18434164, compound

Participants

Reaction Conditions

Reaction Steps

Aa) A solution of 5.6 ml of 2-fluoroanisole in 60 ml of absolute THF is cooled to -78° C. and treated within 15 min. with 31.3 ml of 1.6M butyllithium in hexane. After 15 min. 8.7 g of 1,1,4,7,7-pentamethyldiethylenetriamine are added dropwise and, after a further 2 hrs. at -78° C., 9.4 ml of methyl iodide are added dropwise. The mixture is stirred at -78° C. overnight, then evaporated and taken up in ether/1N hydrochloric acid. The aqueous phase is extracted with ether and the organic phase is dried over sodium sulphate and evaporated in order to give crude 2-fluoro-3-methyl-anisole. 30 ml of nitrobenzene are cooled in an ice bath and then treated in succession with 8.1 g of aluminium chloride and 11.9 g of 4-bromobenzoyl chloride in 9 ml of nitrobenzene at a maximum 6° C. The mixture is stirred and then the 2-fluoro-3-methyl-anisole is added in such a manner that the temperature does not rise above 6° C. The solution is left to warm to room temperature overnight, poured into ice-water/ ethyl acetate and washed with 10% aqueous sodium chloride solution, dried and concentrated. After chromatography over silica gel with hexane/ether (95/5) as the eluent and crystallization from hexane there are obtained 4.0 g of (4-bromo-phenyl)-(3-fluoro-4-methoxy-2-methyl-phenyl)-methanone, m.p. 93-95° C.

Provenance & Evidence