Methoxymethyl-triphenylphosphonium chloride → 4-(3-Fluoro-4-methylphenyl)-3,3-dimethylbutanal

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Reaction Steps

Lithium bis(trimethylsilyl)amide solution (55 ml, 55 mmol, 1M in THF) was added to a mixture methoxy methyl triphenyl phosphonium chloride (18.9 g, 55 mmol) in 65 ml THF dropwise at 0° C. and stirred for 15 min and it was added to a mixture of the product of STEP 3 (7.3 g, 34.7 mmol ) in 35 ml THF dropwise at 0° C. After 5 min, the reaction was quenched with H2O. The product was extracted with ethyl acetate. The aqueous layer was extracted with ethyl acetate. The combined organic layer was washed with H2O, brine, dried with Na0.2SO4, and concentrated. The residue was purified by chromatography (on silica gel, ethyl acetate/hexane=5/95) to give a yellow liquid in 6.3 g. It was dissolved in 100 ml THF and 100 ml 2N HCl. The reaction was heated at reflux for 30 min and cooled to room temperature. THF was evaporated. The product was extracted with ethyl acetate and washed H2O. The aqueous layer was extracted with ethyl acetate. The combined organic layer was washed with brine, dried with Na2SO4, and concentrated. The residue was purified by chromatography (on silica gel, ethyl acetate/hexane=15/85) to yield a colorless oil in 3.8 g. NMR spectra of the product were consistent for the proposed structure.

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