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11th March 2012 @ 07:32
This synthesis is based off one put forth by Son et al. (p. 17), and is summarised below:

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Conclusion: methyl 3-formamidothiophene-2-carboxylate was recovered along with starting material with a combined mass of 0.057 g.

Reaction start time: 11am 07/03/2012
Ethyl-3-aminothiophene-2-carboxylate (0.376 g, 2.39 mmol, 1 equiv.) was dissolved in formamide (1 mL, 25.15 mmol, ~10 equiv.) and heated to 180 °C. TLC at +6.5 hr showed some new products being formed.

TLC (10% ethyl acetate/hexane): + 6.5 hr, visualised with UV/vanillin
JRC8-1(530pm).JPG


Reaction was cooled to rt and left for 36 hr. The mixture was filtered, with no solid product recovered. The mixture was extracted once with ethyl acetate (10mL) and the organic layer was washed twice with water (10mL) and twice with brine (10mL) before being dried over anhydrous magnesium sulfate. The solvent was removed under reduced pressure to yield 0.057 g red solid, and 1H-NMR was taken, revealing a mixture of starting material and a product consistent with the following structure:

2163.png
methyl 3-formamidothiophene-2-carboxylate

1H-NMR:

This red soild was purified by column chromatography using 60% ethyl acetate/hexane as the eluent. Three fractions were collected:

Fraction 1: 0.037 g 1H-NMR showed this to be mostly starting material
1H-NMR:
1.zip
JRC8-1f1.pdf


Fraction 2: 0.004 g 1H-NMR revealed this to be methyl 3-formamidothiophene-2-carboxylate.

1H-NMR:
2.zip
JRC8-1f2.pdf


Fraction 3: 0.056 g 1H-NMR revealed this to be a mixture of solvents and a very small amount of methyl 3-formamidothiophene-2-carboxylate.

1H-NMR:
3.zip
JRC8-1f3.pdf


An accurate yield was not obtained due to a column that did not give good separation, and due to the low crude yield.

Risk Assessment: (paper copy signed)
JRC8-1RA.pdf


References:
Son, J.B.; Jung, S. H.; Choi, W.I.; Jung, Y.H.; Choi, J.Y.; Song, J.Y.; Lee, K.H.; Lee, J.C.; Kim, E.Y.; Ahn, Y.G.; Kim, M.S.; Choi, HG.; Sim, T.B.; Ham, Y.J.; Park, D.; Kim, H.; Kim, D. (Hanmi Holdings Co., Ltd., S. Korea; Korea Institute of Science and Technology; Catholic University Industry Academic Cooperation Foundation). Preparation of thienopyrimidine derivatives for use as protein kinase inhibitors. World Intellectual Property Organisation 2011093684 A2, 2011; SciFinder Scholar AN 2011:971406 (accessed 3/2/2012).
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Attached Files
JRC8-1.png
JRC8-1(530pm).JPG
JRC8-1RA.pdf
1.zip
JRC8-1f1.pdf
2.zip
JRC8-1f2.pdf
3.zip
JRC8-1f3.pdf