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19th July 2012 @ 08:46
After it looked like MNR40-4 went to completion after 1 hour it was decided to monitor the reaction over the first hour. Increasing equivalents of reagents was also investigated.


To a solution of MNR42-1 (0.5 g, 1.59 mmol) in dry acetonitrile (47 mL, HPLC grade stored over 3 Å molecular sieves for 24 hours) and 3 Å molecular sieves (10 g, dried in microwave) under argon at -10 C, was added was added acetyl chloride (0.23 mL, 3.18 mmol), 2,6-lutidine (0.37 mL, 3.18 mmol, stored over 3 Å molecular sieves) and diphenylmethane (0.27 mL, 0.268 mmol). Yb(OTf)3 (0.049 g, 0.08 mmol) was added and the reaction was stirred at ambient temperature (~15 °C).

The reaction was monitored by LCMS by taking samples every 10 minutes carrying out the following procedure.

0.1 ml was removed from the reaction mixture using a disposable syringe and transferred to a vial. EtOAc (0.2 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

5 mins
10 mins
20 mins
30 mins
40 mins
50 mins
60 mins

Plotting the relative peak area of the product against time showed the reaction progressing but after 1 hour the reaction was not completed. Monitoring stopped at this stage due to the time in the evening but this shows that we've a working assay to follow the reaction. reaction needs to be repeated over a longer time to see completion.

Attached Files
mnr41-5 table.PNG