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26th September 2012 @ 05:42
Mnr: 41-50
re-synthesis of MNR46 to try and get a clean sample for characterisation and HPLC analysis

MNR46-1%20scheme.png
mnr46-13%20table.PNG

Hazard Assessment
HIRAC MNR41_47_48.pdf


Procedure
To a solution of KAB22-1 (0.60 g, 2.36 mmol) in HPLC grade acetonitrile (25 mL) under argon at 0 °C , was added was added acetyl chloride (0.30 mL, 4.25 mmol), lutidine (0.38 mL, 3.30 mmol) and Yb(OTf)3 (0.146 g, 0.24 mmol). The reaction was then stirred at room temperature for 16 hours and then the mixture was washed saturated sodium bicarbonate solution (20 mL) and the aqueous layer was extracted with ethyl acetate (3 × 25 mL). The organic fractions were combined and washed with citric acid (10%) (30 mL). The organic fraction was then dried over MgSO4, filtered and concentrated under reduced pressure to yield a yellow oil (0.857 g, 122%)

Column using 30-40% EtOAC/Hex.

Product eluted (by TLC) between fractions 15 and 35 but to test purity of the samples early and late fractions were kept separate.

Fracs 15-20 - 0.140 g

Fracs 21-30 - 0.202 g

Fracs 31-35 - 0.018 g

Fractions 15-20 and 31-35 were immediately vac'd down and dried under high vacuum. 1H NMR of 15-20 showed clean product. 1H NMR of 31-35 was messy.

1H NMR

Frac 15-20 - Clean product
mnr46-13_frac15-20_1H.pdf
mnr46-13_frac15-20.zip


Frac 31-35 - messy
mnr46-13_frac31-35_1H.pdf
mnr46-13_frac31-35.zip


The remaining fractions containing product (fracs 21-30) we combined but not concentrated to complete dryness on the day of running the column due to time. Upon drying, 1H NMR showed only hydrolysis products.

Frac 21-30
mnr46-13_frac21-30_1H.pdf
mnr46-13_frac21-30.zip


This is unusual as the hydrolysis products run higher on TLC and came off before fraction 15. Also, it's exclusively mono-Ac amine where as the higher running spot contains di-Ac amine.

Frac 1-11
mnr46-13_frac1-11_friday.pdf
mnr46-13_frac1-11.zip


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Monday, 2nd October 2012
TLC of the three batches of fractions spotted against MNR46-4 (still product by NMR) showed none of the 3 batches contained product any more.

SANY0334.JPG


running a new sample of MNR46-13 fracs 15-20 confirmed this

mnr46-13_frac15-20_monday.pdf
mnr46-13_f15-20_monday.zip


Conclusions

Using Yb(OTf)3 under catalytic conditions the reaction goes to completion in 16 hours. However, it has become clear that the product can decompose back to the relevant aldehyde and mono-Ac amine. This appears to take place in solvent but at this stage it's unclear the rate of this reverse reaction.

MNR46-13%20decomp%20scheme.png
Linked Posts
Attached Files
mnr46-13 table.PNG
mnr46-13_frac15-20.zip
mnr46-13_frac31-35.zip
mnr46-13_f15-20_monday.zip
mnr46-13_frac15-20_1H.pdf
mnr46-13_frac31-35_1H.pdf
mnr46-13_frac21-30_1H.pdf
mnr46-13_frac21-30.zip
mnr46-13_frac1-11.zip
mnr46-13_frac1-11_friday.pdf
SANY0334.JPG
MNR46-13 decomp scheme.png
mnr46-13_frac15-20_monday.pdf