B. Cottineau, D. F. O’Shea / Tetrahedron 63 (2007) 10354–10362
10361
1
plate): 2951, 2937, 2903, 1606 cmꢀ1. H NMR (300 MHz,
CDCl3): d 0.94 (s, 9H), 2.34 (s, 3H), 2.40 (s, 3H), 2.54 (s,
2H), 3.75 (s, 3H), 7.54 (s, 1H), 8.03 (s, 1H). 13C NMR
(75 MHz, CDCl3): d 11.3, 18.8, 28.2, 30.1, 34.1, 38.3,
107.5, 121.9, 123.8, 127.1, 135.5, 142.0, 146.4. ES+-MS:
m/z 231 (M+H)+. HRMS: found (M+H)+ 231.1853.
C15H23N2 requires 231.1861. Anal. Calcd for C15H22N2:
C, 78.21; H, 9.63; N, 12.16. Found: C, 78.20; H, 9.88; N,
11.99.
3. (a) Hogan, A.-M. L.; O’Shea, D. F. J. Am. Chem. Soc. 2006,
128, 10360; (b) Kessler, A.; Coleman, C. M.; Charoenying,
P.; O’Shea, D. F. J. Org. Chem. 2004, 69, 7836; (c) Coleman,
C. M.; O’Shea, D. F. J. Am. Chem. Soc. 2003, 125, 4054.
4. Hogan, A.-M. L.; O’Shea, D. F. Org. Lett. 2006, 8, 3769.
5. McKinley, N. F.; O’Shea, D. F. J. Org. Chem. 2006, 71, 9552.
6. Cottineau, B.; O’Shea, D. F. Tetrahedron Lett. 2005, 46,
1935.
ꢀ
7. (a) Popowycz, F.; Routier, S.; Joseph, B.; Merour, J.-Y.
Tetrahedron 2007, 63, 1031; (b) Merour, J.-Y.; Joseph, B.
ꢀ
Curr. Org. Chem. 2001, 5, 471.
4.1.6. N-[3-(1-Benzoyl-3,3-dimethyl-butyl)-pyridin-2-yl]-
2,2-dimethyl-propionamide 11. A stirred solution of 5a
(0.05 g, 0.24 mmol) in dry diethyl ether (5 mL) at ꢀ78 ꢁC
under nitrogen was treated dropwise with phenyllithium
(0.27 mL of a 1.35 M solution, 0.37 mmol). The reaction
mixture was warmed to ꢀ30 ꢁC, stirred at this temperature
for 1 h and cooled to ꢀ78 ꢁC. tert-Butyllithium (0.32 mL
of a 1.15 M solution, 0.37 mmol) was added over 10 min
and the reaction mixture was stirred at ꢀ78 ꢁC for a further
1 h. Benzonitrile (0.06 mL, 0.61 mmol) was added and the
reaction mixture was warmed to 0 ꢁC and stirred for 1 h.
Aqueous HCl (2 M, 3 mL) was added and the reaction mix-
ture was warmed to room temperature, stirred for 20 min and
slowly added over 10 min to a saturated potassium carbonate
solution (20 mL). The solution was extracted with diethyl
ether (2ꢂ25 mL), dried over Na2SO4 and concentrated un-
der reduced pressure. The residue was purified by silica
gel column chromatography with diethyl ether/cyclohexane
(7:3) as eluent yielding 11 as a colourless solid (80%), mp
68–69 ꢁC. IR (KBr plate): 3218, 3168, 3062, 2958,
8. (a) Wu, P.-W.; Hsieh, W.-T.; Cheng, Y.-M.; Wei, C.-Y.; Chou,
P.-T. J. Am. Chem. Soc. 2006, 128, 14426; (b) Rich, R. L.;
Gai, F.; Lane, J. W.; Petrich, J. W.; Schwabacher, A. W.
J. Am. Chem. Soc. 1995, 117, 733.
ꢀ
9. For examples, see; (a) Henon, H.; Messaoudi, S.; Anizon, F.;
Aboab, B.; Kucharczyk, N.; Leonce, S.; Golsteyn, R. M.;
ꢀ
Pfeiffer, B.; Prudhomme, M. Eur. J. Pharmacol. 2007, 554,
106; (b) Cai, Z.; Feng, J.; Guo, Y.; Li, P.; Shen, Z.; Chu, F.;
Guo, Z. Bioorg. Med. Chem. 2006, 14, 866; (c) Fonquerna,
S.; Miralpeix, M.; Pages, L.; Puig, C.; Cardus, A.; Anton, F.;
Vilella, D.; Aparici, M.; Prieto, J.; Warrellow, G.; Beleta, J.;
Ryder, H. Bioorg. Med. Chem. Lett. 2005, 15, 1165; (d)
Messaoudi, S.; Anizon, F.; Pfeiffer, B.; Golsteyn, R.;
Prudhomme, M. Tetrahedron Lett. 2004, 45, 4643; (e)
ꢀ
ꢀ
ꢀ
Marminon, C.; Pierre, A.; Pfeiffer, B.; Perez, V.; Leonce, S.;
Joubert, A.; Bailly, C.; Renard, P.; Hickman, J.; Prudhomme,
M. J. Med. Chem. 2003, 46, 609; (f) Kuo, G.-H.; Prouty, C.;
DeAngelis, A.; Shen, L.; O’Neill, D. J.; Shah, C.; Connolly,
P. J.; Murray, W. V.; Conway, B. R.; Cheung, P.; Westover,
L.; Xu, J. Z.; Look, R. A.; Demarest, K. T.; Emanuel, S.;
Middleton, S. A.; Jolliffe, L.; Beavers, M. P.; Chen, X.
J. Med. Chem. 2003, 46, 4021; (g) Cooper, L. C.; Chicchi,
G. G.; Dinnell, K.; Elliott, J. M.; Hollingworth, G. J.; Kurtz,
M. M.; Locker, K. L.; Morrison, D.; Shaw, D. E.;
Tsao, K.-L.; Watt, A. P.; Williams, A. R.; Swain, C. J.
Bioorg. Med. Chem. Lett. 2001, 11, 1233.
1
1680 cmꢀ1. H NMR (300 MHz, CDCl3): d 0.87 (s, 9H),
1.41 (s, 9H), 1.80 (dd, J¼5.1, 13.9 Hz, 1H), 2.39 (dd,
J¼7.5, 13.9 Hz, 1H), 4.87 (dd, J¼5.1, 7.5 Hz, 1H), 7.14
(dd, J¼4.8, 7.8 Hz, 1H), 7.45–7.50 (m, 2H), 7.56–7.61 (m,
1H), 7.88 (dd, J¼1.5, 7.8 Hz, 1H), 8.04–8.08 (m, 2H),
8.29 (dd, J¼1.5, 4.8 Hz, 1H), 8.6 (br s, 1H). 13C NMR
(75 MHz, CDCl3): d 27.6, 30.0, 31.6, 39.8, 45.0, 46.1,
121.8, 128.68, 128.70, 131.5, 133.3, 136.3, 146.8, 148.8,
178.9, 200.8. ES+-MS: m/z 367 (M+H)+. HRMS: found
(M+H)+ 367.2402. C23H31N2O2 requires 367.2386. Anal.
Calcd for C23H30N2O2: C, 75.37; H, 8.25; N, 7.64. Found:
C, 75.12; H, 8.31; N, 7.53.
10. (a) Martin, M. J.; Trudell, M. L.; Arauzo, H. D.; Allen, M. S.;
LaLoggia, A. J.; Deng, L.; Schultz, C. A.; Tan, Y.-C.; Bi, Y.;
Narayanan, K.; Durn, L. J.; Koelher, K. F.; Skolnick, P.;
Cook, J. M. J. Med. Chem. 1992, 35, 4105; (b) Tan, Y.-C.;
Trudell, M. L.; Cook, J. M. Heterocycles 1998, 27, 1607; (c)
Mann, F. G.; Prior, A. F.; Willcox, T. J. J. Chem. Soc. 1959,
3830.
11. (a) Hands, D.; Bishop, B.; Cameron, M.; Edwards, J. S.;
Cottrell, I. F.; Wright, S. H. B. Synthesis 1996, 877; (b)
Meade, E. A.; Beauchamp, L. M. J. Heterocycl. Chem. 1996,
33, 303.
12. (a) Cacchi, S.; Fabrizi, G.; Parisi, L. M. J. Comb. Chem. 2005,
2, 510; (b) Amjad, M.; Knight, D. W. Tetrahedron Lett. 2004,
45, 539; (c) Koradin, C.; Dohle, W.; Rodriguez, A. L.;
Schmid, B.; Knochel, P. Tetrahedron 2003, 59, 1571;
(d) Kumar, V.; Dority, J. A.; Bacon, E. R.; Singh, B.; Lesher,
G. Y. J. Org. Chem. 1992, 57, 6995; (e) Ujjainwalla, F.;
Warner, D. Tetrahedron Lett. 1998, 39, 5355; (f) Park, S. S.;
Choi, J.-K.; Yum, E. K. Tetrahedron Lett. 1998, 39, 627.
13. (a) Lachance, N.; April, M.; Joly, M.-A. Synthesis 2005, 2571;
Acknowledgements
This work was supported by a research grants from Enter-
prise Ireland and the Program for Research in Third-Level
Institutions administered by the HEA. We thank Dr. D. Rai
of the CSCB Mass Spectrometry Centre for analysis and
Dr. H. Mueller-Bunz for X-ray crystallographic service.
References and notes
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ꢀ
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