Hexane → 2-Fluoro-1,3-bis(methoxymethoxy)-4-methyl-benzene

Participants

Reaction Steps

To a solution of 2,4-bis(methoxymethoxy)-1-methyl-benzene (WO2012/076877 Intermediate 150, 2000 mg, 9.4233 mmol) in dry THF (20 mL) butyllithium 1.6M in hexane (6.77 ml, 10.84 mmol) was slowly added and the reaction mixture was stirred for 30 minutes at room temperature. The reaction was cooled to −15° C. and it was added (via cannulation) to a solution of N-(benzenesulfonyl)-N-fluoro-benzenesulfonamide (3565.8 mg, 11.308 mmol) in dry THF (10 mL) at −15° C. The reaction mixture was stirred for 30 minutes at the same temperature. The reaction was quenched with brine (5 ml) diluted with water (20 ml) and extracted with ethyl acetate (2×30 ml). The organic layer was dried (Na2SO4), filtered and evaporated and the residue was purified by flash chromatography (Biotage system) on silica gel using a SNAP 50 g as column and cyclohexane/ethyl acetate from 100:0 to 80:20 as eluent affording the title compound (1950 mg) as colourless oil.

Provenance & Evidence