E.K. Raja, D.A. Klumpp / Tetrahedron 67 (2011) 4494e4497
4497
4.2. General preparation of the ketones
4.3.3. N-((3-Methylpyridin-2-yl)(phenyl)methyl)acetamide
22. Yield 20% as a viscous, colorless oil. 1H NMR (CDCl3, 500 MHz)
The amino-nitrile (1 mmol) is dissolved in dry CH2Cl2 (5 mL) to
which is added benzene (2 mL). With stirring, triflic acid (2 mL) is
then slowly added and the reaction mixture is stirred overnight at
60e80 ꢁC. The mixture is then quenched by pouring the solution
over ice/water. The aqueous solution is then made basic by slow
addition of 10 M NaOH and the solution is extracted twice with
chloroform. The organic layer is washed with water, brine
(2ꢂ20 mL) and dried over anhydrous sodium sulfate. In the event
that imine/ketone mixtures are obtained, it may be necessary to stir
the triflic acid/ice/water mixture for few hours in order to ensure
complete hydrolysis. The products are purified via column chro-
matography (silica gel; hexanes/ether).
d
2.07 (s, 3H), 2.26 (s, 3H), 6.34 (d, 1H, J¼8 Hz), 7.19e7.26 (m, 2H),
7.29e7.34 (m, 2H), 7.48 (dd, 1H, J¼0.5, 7.5 Hz), 7.91 (d, 1H, J¼7 Hz),
8.48 (dd, 1H, J¼1.0, 5.0 Hz). 13C NMR (CDCl3, 500 MHz)
d 18.2, 23.5,
53.8, 122.7, 127.5, 128.2, 128.5, 131.3, 138.9, 140.6, 145.7, 156.6, 169.1.
Low resolution mass spectrum (EI): m/z: 240 (Mþ), 197, 181, 147,
106, 43. Anal. Calcd for C15H16N2O: C, 74.97; H, 6.71; N, 11.66.
Found: C, 72.72; H, 6.82; N, 10.79.
Acknowledgements
We gratefully acknowledge the support of the National Science
Foundation (CHE-0749907) and the NIH-National Institute of
General Medical Sciences (GM085736-01A1).
4.3. General preparation of the amides
Using the same procedure, the triflic acid-promoted reaction is
conducted and then the mixture is cooled in an ice bath and
a methanolic solution (10 mL) of NaBH4 (5 mmol) is added (argon
atmosphere). The solution is left to stir overnight at room tem-
perature. The mixture is then poured over ice/water and made basic
by slow addition of 10 M NaOH. The solution is extracted twice with
chloroform. The organic layer is washed with water, brine
(2ꢂ20 mL) and dried over anhydrous sodium sulfate. The amine is
further acylated by direct addition of acetic anhydride (1 mmol).
The products are purified via column chromatography (silica gel;
hexanes/ether).
Supplementary data
Computational methods and results, characterization data, and
spectra of compounds are associated with this article as supple-
mentary data. Supplementary data associated with this article can
References and notes
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4.3.1. N-Ethyl-N-(3-oxo-3-phenylpropyl)acetamide 11. Yield 98% as
a viscous, yellow oil. 1H NMR (CDCl3, 300 MHz; mixture of cis/trans
isomers) minor component:
d
1.12 (t, 3H, J¼4.2 Hz), 2.12 (s, 3H),
3.25 (t, 3H, J¼4.2 Hz), 3.40 (q, 2H, J¼4.2 Hz), 3.73 (t, 3H, J¼4.2 Hz),
7.45e7.49 (m, 2H), 7.56e7.60 (m, 1H), 7.92e7.94 (m, 2H); major
component:
d
1.18 (t, 3H, J¼4.2 Hz), 2.07 (s, 3H), 3.30 (t, 3H,
J¼4.2 Hz), 3.37 (q, 2H, J¼4.2 Hz), 3.68 (t, 3H, J¼4.2 Hz), 7.42e7.45
(m, 2H), 7.53e7.56 (m, 1H), 7.95e7.97 (m, 2H). 13C NMR (CDCl3,
5. Chung, F.; Tisne, C.; Lecourt, T.; Dardel, F.; Micouin, L. Angew. Chem., Int. Ed.
300 MHz; mixture of cis/trans isomers) minor component:
21.5, 37.4, 40.4, 43.3, 127.9, 128.8, 133.4, 136.5, 170.4, 197.8; major
d 12.9,
2007, 46, 4489.
6. (a) Leclerc, E.; Vrancken, E.; Mangeney, P. J. Org. Chem. 2002, 67, 8928; (b)
Weiberth, F. J.; Hall, S. S. J. Org. Chem. 1986, 51, 5338.
component:
d 14.1, 21.4, 37.3, 42.0, 44.5, 128.1, 128.6, 133.3, 136.7,
7. Pankratov, V. A.; Chesnokova, A. E. Russ. Chem. Rev. 1989, 58, 879.
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Millam, J. M.; Iyengar, S. S.; Tomasi, J.; Barone, V.; Mennucci, B.; Cossi, M.;
Scalmani, G.; Rega, N.; Petersson, G. A.; Nakatsuji, H.; Hada, M.; Ehara, M.;
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Done Using Gaussian 03, Revision C.02; Gaussian: Wallingford CT, 2004.
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170.6, 199.2. Low resolution mass spectrum (EI) m/z: 219 (Mþ), 176,
105, 77, 58. High resolution mass spectrum, calcd for C13H17O2N,
219.12593, found 219.12710.
4.3.2. N-(2-(Acetamido(phenyl)methyl)phenyl)acetamide 20. Yield
22% as a light yellow solid, mp: 178e180 ꢁC. 1H NMR (CDCl3,
500 MHz)
d 2.16 (s, 3H), 2.24 (s, 3H), 2.54 (s, 1H), 6.61 (d, 1H,
J¼9.5 Hz), 6.98e7.00 (m, 2H), 7.08 (t, 1H, J¼7.5 Hz), 7.30e7.45 (m,
4H), 7.95 (d, 1H, J¼8 Hz), 9.16 (s, 1H). 13C NMR (CDCl3, 500 MHz)
d
23.2, 24.2, 51.5, 124.9, 125.2, 126.3, 126.9, 127.6, 128.5, 128.7, 128.8,
133.8, 134.8, 136.3, 139.4, 169.7, 170.9. Low resolution mass spec-
trum (EI) m/z: 283 (Mþ), 264, 239, 222, 197, 180, 164, 145, 119, 104,
77, 62, 43. High resolution mass spectrum, calcd for C17H18O2N2,
282.13683, found 282.13759.
10. Olah, G. A.; Kiovsky, T. E. J. Am. Chem. Soc. 1968, 90, 4666.