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9th January 2012 @ 04:55

Acid-mediated Pictet-Spengler of MW51 to give N-benzoyl-derivative of PZQ MNR14-1 cont'

Acid-mediated Pictet-Spengler of KAB6-1to give N-benzoyl-derivative of PZQ MNR14-2

Hazard and Risk Assessment: As for MNR12-2

ProcedureKAB6-1 (0.59 g, 0.28 mmol) was stirred with methanesulfonic acid (8 mL, 123 mmol, 83 eq (the bottle ran out) at room temperature and after 1 hour (first TLC) all the starting material had been consumed. The reaction was quenched with saturated sodium carbonate and extracted with EtOAc (20 mL x2). The organic fractions were dried over magnesium sulfate, filtered and concentrated under reduced pressure.

Crude - 0.558 g as a dark orange oil.

Column 50-75% EtoAc/Hex

Frac 4-11, 0.188 g - MNR14-2-INT 1H NMR MNR14-2-INT Frac 24-34 0.205 g - MNR14-2 product 1H NMR MNR14-2

Although no intermediate showed up on the TLC of the mini workup at 1 hour, almost 50% of material isolated off the column was MNR14-2-INT. I think this can be put down to the fact that the starting material was very viscous and getting it into the flask was difficult. As a result some starting material remained stuck to the walls of the flask and did not get the appropriate contact with the acid. Also, this did not show up on the TLC as the sample for the mini workup was taken from the reaction solution. It can only be assumed that the time it took to rinse and quench the reaction was enough to consume the unreacted starting material to intermediate but a longer reaction time is required to push the second cyclisation.

 

IR 

1c rac IR MNR14-2.jpg
Attached Files
MNR14-2 scheme.png
MNR14-2 table.PNG
mnr14-2_frac4-11_MeOH.pdf
mnr14-2_frac24-34_MeOH.pdf
mnr14-2_frac4-11_MeOH.zip
mnr14-2_frac24-34.zip
mnr14-2_frac24-34_MeOH.zip
MNR14-2_INT.png
MNR14-2_INT.png
1c rac IR MNR14-2.jpg