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ChemComm
Page 4 of 4
DOI: 10.1039/C6CC09023K
COMMUNICATION
Journal Name
Furthermore, although the unsubstituted methyl benzoate
proved relatively unreactive under the reaction conditions (see
ESI), the electron-deficient 4-nitro derivative was successfully
converted into 7i using 10 mol% acetic acid. However, a high
reaction temperature of 150 °C was required in order to afford
the product in good yield. An increased catalyst loading was
not employed as this resulted in the production of a larger
proportion of the acetamide side product.
Notes and references
We are grateful for the financial support received from the
EPSRC during this research project.
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a
b
Isolated yields. Reaction conditions: ethyl ester (2 equiv.), AcOH (10 mol%),
110 °C, 20 h. c Reaction conditions: ethyl formate (2 M), AcOH or formic acid (50
d
mol%), 20 °C, 16 h. Reaction conditions: ethyl trifluoroacetate (1 equiv.), no
catalyst, 25 °C, 20 h. e Can also be performed in toluene (2 M). f As determined by
g
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chiral HPLC analysis. Reaction conditions: methyl 4-nitrobenzoate (1 equiv.),
h
AcOH (10 mol%), 150 °C, 20 h. Reaction conditions: Boc-Gly-OMe (1 equiv.),
AcOH (10 mol%), 110 °C, 20 h.
In summary, we have identified acetic acid as an effective
catalyst for the N-acetylation of amines, using either ethyl
acetate or butyl acetate as the acyl source. The methodology
has been shown to transform a wide variety of amines into
their acetamide products in excellent yields. The methodology
can also be applied to other esters, including formates,
electron-deficient benzoates and amino acid esters, in order to
synthesise higher amides.
4 | J. Name., 2012, 00, 1-3
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