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1st August 2012 @ 02:44
Monitoring reaction at -30 C with the idea that maybe complexes will be more stable at these temperatures and catalyse the reaction ahead of free Yb(OTf)3.

MNR41-4%20scheme.png
mnr41-8%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 -30 °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). Yb(OTf)3 solution (0.128 g, in THF (15 mL)) (2.3 mL, 0.02 g, 0.03 mmol) was added and the reaction was stirred at -30 and followed by LCMS analysis.

The reaction was monitored by LCMS by taking samples carrying out the following procedure.

0.1 ml was removed from the reaction mixture using a disposable syringe and transferred to a vial. EtOAc (0.4 mL) and sodium hydrogen carbonate saturated solution (0.2 mL) was added and the vial capped and shaken. The layers were allowed to separate and the organic layer was carefully removed by pipette and transferred to another vial and concentrated to dryness under reduced pressure.

Acetonitrile (1.8 mL) was added and the mixture shaken, 0.02 mL was transferred to a LCMS vial and acetonitrile 0.4 mL).

Samples taken at

30 mins
60 mins
90 mins
135 mins
180 mins
240 mins
300 mins
400 mins
1320 mins
1440 min (24 hours)
1620 min (24 + 3)

At 24 hours the reaction was allowed to reach -10 °C.

Plotting the relative peak area of the product against time showed the following.

mnr41-8_plot.PNG

Initial product was formed as the reaction was going to be left to stand in the freezer but it was found that the freezer was only at -10 °C therefore the reaction was allowed to warm for approximately 30 minutes before the cryocooler could get set up and to temperature. Once the reaction temperature was stable again at -30 °C it can be seen that as good as no reaction was taking place. At the 24 hour mark the cryocooler was adjusted to -10 °C and the reaction allowed to continue. The acetone bath took approximately 3 hours to rise to -10 °C during which time the reaction was found to proceed but not to completion. After 7 hours the reaction was still not complete and had to be left over night. In the morning, 23 hours after adjusting the temperature the reaction was found to be complete and by LCMS at a yield >95%

This reaction needs to be repeated and followed at -10 °C over approximately 10 hours.

Lab book page complete, MNR
Attached Files
mnr41-8 table.PNG
mnr41-8_plot.PNG
mnr41-8_48hours.pdf
mnr41-8_47hours.pdf
mnr41-8_03hours.pdf
mnr41-8_29hours.pdf
mnr41-8_01hours.pdf
mnr41-8_04 hours.pdf
mnr41-8_27hours.pdf
mnr41-8_31hours.pdf