Methoxymethyl-triphenylphosphonium chloride → 5-(4,4,4-Trifluoro-1-methoxymethylene-butyl)-2-(4-trifluoromethyl-phenyl)-pyridine

Methoxymethyltriphenylphosphonium chloride (7.4 g, 21.6 mmol) is suspended in anhydrous toluene (25 mL) and potassium tert-butoxide (2.4 g, 21.6 mmol) is added at room temperature in one portion. The mixture is allowed to stir under nitrogen for 1 h. Meanwhile, 4,4,4-Trifluoro-1-[6-(4-trifluoromethyl-phenyl)-pyridin-3-yl]-butan-1-one (5.0 g, 14.4 mmol) is dissolved in another portion of the toluene (25 mL), and kept at room temperature. The mixture is then cooled to 0° C. with ice water, and then the ketone is transferred by cannula. The reaction is allowed to stir at 0° C. for 10 min, then the ice bath is removed. The reaction is allowed to warm to room temperature and monitored by HPLC. Upon complete conversion, the reaction is carefully quenched with saturated ammonium chloride solution, and diluted with ethyl acetate, then extracted. The organic layer is washed with water and brine, dried over anhydrous sodium sulfate, then filtered and concentrated. The 5-(4,4,4-Trifluoro-1-methoxymethylene-butyl)-2-(4-trifluoromethyl-phenyl)-pyridine (4.1 g, 10.9 mmol) is isolated as a mixture of regioisomers after column chromatography, 76% yield.

1. customkept at room temperature
2. stirringto stir at 0° C. for 10 min
3. customthe ice bath is removed
4. customUpon complete conversion, the reaction is carefully quenched with saturated ammonium chloride solution
5. additiondiluted with ethyl acetate
6. extractionextracted
7. washThe organic layer is washed with water and brine
8. dry with materialdried over anhydrous sodium sulfate
9. filtrationfiltered
10. concentrationconcentrated

ORD record

ord-8ca8966499164488afebb657ea266451

Source dataset

uspto-grants-2011_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07989457B2