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4th July 2012 @ 10:35
Synthesis of MNR40-1 - reaction time 38 hours

MNR41-4%20scheme.png

HIRAC
HIRAC MNR41.pdf


Procedure

To a solution of KAB23-2 (0.10 g, 0.32 mmol) in dry acetonitrile (10 mL, Sigma sure/seal) and 3 Å molecular sieves (2 g, dried in microwave) under argon, was added was added acetyl chloride (0.02 mL, 0.32 mmol) and 2,6-lutidine (0.04 mL, 0.32 mmol, stored over 3 Å molecular sieves). Yb(OTf)3 (0.01 g, 0.02 mmol, 0.05 equiv) was added and the reaction was stirred at ambient temperature (~15 °C) for 38 hours.

The mixture was filtered to remove the molecular sieves and washed with EtOAc (5 mL). The filtrate was washed with saturated sodium bicarbonate solution (10 mL). The aqueous layer was extracted with ethyl acetate (3 × 15 mL). The organic fractions were combined, dried over MgSO4, filtered and concentrated under reduced pressure to yield a yellow oil that partially crystallised on standing (0.111 g).

Column - 50-100% EtOAc/Hex

Frac 3-20 0.038 g - 5:1 mixture of 4-Nitrobenzaldehyde and starting material.
Frac 38-60 0.37 g - product with slight impurities. 0.104 mmol, 34%

hydrolysis of starting material back to 4-Nitrobenzaldehyde, reaction not dry enough. Must dry glassware longer and use drier solvent.


In an attempt to develop an LC assay, calibration curves of the peak area of the LCMS traces were prerared.

Serial dilutions of SM and Product was carried out to get LCMS samples of known concentrations at 50 ug/mL
calcs1.png

Further dilutions were carried out to give a variety of known concentration samples less than 50 ug/mL

dilutions.PNG

Data to be plotted

plot%20data.PNG

Plotting starting material as Moles vs Peak area
kab23-2_LCMS.png

Plotting product material as Moles vs Peak area
kab26-2_LCMS.png

The peak of the product appears to be more sensitive to concentration change and looks to be more reliable to monitor. There is still good separation between SM and product so when following a reaction it should be possible to to consumption of starting material and formation of product. LC traces of the by-products has yet to be carried out.

Data

mixture of 89% SM and 11% Prod
kab23-2-89.pdf

mixture of 75% SM and 25% Prod
kab23-2-75.pdf

mixture of 50% SM and 50% Prod
kab23-2-50.pdf

mixture of 25% SM and 75% Prod
kab23-2-25.pdf

5% Prod
kab26-2-05.pdf

100% Prod
kab26-2_100.pdf
Attached Files
kab23-2_LCMS.png
kab26-2_LCMS.png
plot data.PNG
calcs1.png
dilutions.PNG
kab26-2_100.pdf
kab23-2-75.pdf
kab26-2-05.pdf
kab23-2-89.pdf
kab23-2-25.pdf
kab23-2-50.pdf
HIRAC MNR41.pdf
HIRAC MNR41.pdf