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8th August 2012 @ 02:50
Control reaction testing the standard reaction conditions (25 °C over 1 hour) without the addition of catalyst.

MNR41-4%20scheme.png
mnr41-13%20table.PNG

To a solution of MNR42-1 (0.2 g, 0.64 mmol) in dry acetonitrile (20 mL, HPLC grade stored over 3 Å molecular sieves for 24 hours) and 3 Å molecular sieves (3 g, dried in microwave) under argon at 0 °C, was added was added acetyl chloride (0.08 mL, 1.15 mmol), 2,6-lutidine (0.10 mL, 0.89 mmol, stored over 3 Å molecular sieves) and PZQ (0.02 g, 0.06 mmol). The reaction was stirred at 25 °C for 1 hour.

After 1 hour a sample was taken for mini workup and LCMS. The reaction was left to stir.

LCMS

mnr41-13_70mins.pdf


Product peak was 93% of the it and standard PZQ therefore referring to >95% conversion within the first hour of reaction.

After 75 minutes a sample was taken for mini workup and LCMS. The reaction was left to shake.

Work Up

The mixture was filtered to remove the molecular sieves and washed with EtOAc (20 mL). The filtrate was washed with saturated sodium bicarbonate solution (25 mL). The aqueous layer was extracted with ethyl acetate (3 × 30 mL). The organic fractions were combined, dried over MgSO4, filtered and concentrated under reduced pressure to yield a yellow solid (0.282 g)

The crude was then taken up in IPA (3 ml) in an attempt to crystallise the product overnight. In the morning, the crystals were washed with IPA.

1st crop - 0.165 g

mnr41-13.jpg


NMR

mnr41-13.pdf


Clean product

Conclusions

* Potential contaminated glassware - traces of Yb in the flask
* Potential for the reaction to be catalysed by the molecular sieves (slightly acidic)
* Potential for traces of metal coming from anther source, spatula, stir bar, needles.

- requires further control experiments testing to above variables
*
Attached Files
mnr41-13 table.PNG
mnr41-13_70mins.pdf
mnr41-13.jpg
mnr41-13.pdf