Methoxymethyl-triphenylphosphonium chloride → 5-Bromo-2-(4-methoxyphenyl)-3-(2-methoxyvinyl)pyrazolo[1,5-a]pyridine

Participants

Reaction Conditions

Reaction Steps

To a solution of methoxymethyltriphenylphosphonium chloride (298 mg, 0.87 mmol) in methanol (3 ml) was added a solution of sodium methoxide 25% wt. in methanol (0.20 ml, 0.87 mmol). The resulting white suspension was stirred at 20° C. for 30 minutes. The mixture was concentrated to dryness and azeotroped with toluene (6 ml) twice. The resulting solid was suspended in toluene (2 ml). A suspension of 5-bromo-2-(4-methoxyphenyl)pyrazolo[1,5-a]pyridine-3-carbaldehyde (180 mg, 0.54 mmol) in toluene (4 ml) was added to the ylide suspension. Heated the resulting mixture to 85-90° C. and stirred for 1.25 h. Cooled to 20° C. and stirred 17.5 h. In a separate flask, to a solution of methoxymethyltriphenylphosphonium chloride (298 mg, 0.87 mmol) in methanol (3 ml) was added a solution of sodium methoxide 25% wt. in methanol (0.20 ml, 0.87 mmol). The resulting white suspension was stirred for 30 minutes, concentrated and azeotroped with toluene (6 ml) twice. The resulting solid was suspended in toluene (2 ml) and added to the reaction mixture which was heated to 90° C. for 2 h at which time monitoring the reaction by LC indicated all starting material had converted to the title compound. to the mixture was cooled to 20° C., filtered through a 0.45 μm filter and rinsed with toluene (2 mL). The filtrate was concentrated under reduced pressure to afford a residue that was purified by automated ISCO chromatography (ethyl acetate/hexane; 25/75). The title compound was obtained as a bright yellow solid (168 mg, 86%). LCMS m/z 359.0 (M+H)+, ret. time=2.31 (cis isomer) and 2.34 min (trans isomer).

Provenance & Evidence