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5663
the solution of ethyl 4-tert-butoxy-3-oxobutanoate (6) (28.9 g, 143.06 mmol,
1 equiv) in CCl4 (75 mL). The reaction mixture was stirred for 1 h at 26 °C. After
1 h, the white solid of succinamide was filtered off and the filtrate was
evaporated in vacuo. The thick liquid thus obtained was used for further
reaction without purification. Thiourea (14.7 g, 193.13 mmol, 1.35 equiv) was
added to crude ethyl 2-bromo-4-tert-butoxy-3-oxobutanoate (30.2 g) at 26 °C.
The neat reaction mixture was then heated to 60–65 °C for 1.5 h. After
completion of the reaction, it was cooled to 26 °C and water was added to it.
The aqueous layer was extracted with DCM (3 Â 150 mL), washed with brine
(50 mL), dried over anhydrous sodium sulfate, filtered and distilled in vacuo. The
crude product was purified by column chromatography using silica gel (100–
200 mesh size) as stationary phase and ethyl acetate:petroleum ether (1:1) as a
mobile phase. (28.79 g, 78% yield): mp 108–110 °C; IR (KBr cmÀ1) 3163, 1701,
1512, 1288, 759; 1H NMR (400 MHz, CDCl3): d (ppm) 5.88 (s, 2H) 4.73 (s, 2H) 4.27
(q, J = 7.2 Hz, 2H), 1.32 (t, J = 7.2 Hz, 3H) 1.29 (s, 9H); 13C NMR (100 MHz, CDCl3) d
(ppm) 170.8, 162.1, 159.5, 111.5, 74.2, 61.1, 58.8, 27.7, 14.4; UPLC purity: 97.1%,
tR 3.12 min; m/z (Relative intensities) (+ve mode) 258.9 (M+H)+, (100%); 280.9
(M+Na)+, (60%). Anal. Calcd for C11H18N2O3S: C, 51.14; H, 7.02; N, 10.84; S, 12.41.
Found: C, 50.97; H, 6.95; N 10.57; S, 12.79.
wise to the reaction mixture at 0–5 °C. The reaction mixture was stirred for
10 min at 0–5 °C and then at 26 °C for 15 h. After completion, the reaction
mixture was diluted with DCM (50 mL), washed with water (15 mL), brine
(10 mL), dried over anhydrous sodium sulfate and filtered. The organic layer
was then concentrated in vacuo to furnish crude product. The crude product
was purified by column chromatography using silica gel (100–200 mesh size)
as stationary phase and ethyl acetate:petroleum ether (2:3) as a mobile phase.
Compound 15b (0.128 g, 36% yield): IR (KBr cmÀ1) 2928, 2854, 1651, 1508,
1280, 760; 1H NMR (400 MHz, DMSO-d6) d (ppm) 13.41 (s, 1H), 13.25 (s, 1H),
8.18 (dd, J1 = 5.6 Hz, J2 = 8.8 Hz, 2H), 7.90 (d, J = 7.6 Hz, 1H), 7.81(t, J = 7.6 Hz,
1H), 7.75–7.67 (m, 2H), 7.36 (t, J = 8.8 Hz, 2H); HPLC purity 99.7%, tR
18.36 min.; ESI-MS m/z (Relative intensities) (+ve mode) 434.9 (M+H)+,
(100%), 466.9 (M+Na)+, (30%).
19. General procedure for preparation of aryl carboxamides (15f–g): Acid (1 equiv)
was dissolved in DCM (3 mL) under N2 atmosphere. Oxalyl chloride (1.5 equiv)
was added dropwise in the reaction mixture at 0 °C. The reaction mixture was
then stirred for 1.5 h at 26 °C. Upon completion, DCM and excess oxalyl
chloride were removed in vacuo. The acid chloride thus prepared was dissolved
in DCM (5 mL) under nitrogen atmosphere. In another round-bottomed flask
amine (14a) (1 equiv) dissolved in DCM (3 mL) was taken and Et3N (2.5 equiv)
was added at 26 °C, stirred for 10 min at the same temperature. The acid
chloride dissolved in DCM (5 mL) was added in drops to the above mixture at
0 °C. The whole reaction mixture was stirred for 2 h at 26 °C. After 2 h, the
reaction mixture was diluted with DCM (50 mL), washed with water (15 mL),
brine (10 mL), dried over anhydrous sodium sulfate and filtered. The organic
layer was concentrated in vacuo to obtain crude product. The crude product
was purified by column chromatography using silica gel (100–200 mesh size)
as stationary phase and ethyl acetate: petroleum ether (2:3) as a mobile phase.
Compound 15f (0.138 g, 38% yield): IR (KBr cmÀ1) 3173, 2926, 1649, 1537,
1171, 746; 1H NMR (400 MHz, DMSO-d6) d (ppm) 13.26 (s, 1H), 13.15 (s, 1H),
7.89 (d, J = 7.6 Hz, 1H), 7.79 (d, J = 7.2 Hz, 1H), 7.74–7.70 (m, 4H), 7.65–7.62 (t,
J = 7.2 Hz, 3H), 3.75 (d, J = 8.8 Hz, 1H), 3.52 (d, J = 11.2 Hz, 1H), 2.39 (t,
J = 11.2 Hz, 1H), 2.24 (t, J = 11.2 Hz, 1H), 1.85–1.82 (m, 1H), 1.43–1.28 (m, 3H),
0.98–0.85 (m, 1H); HPLC purity 95.7%, tR 4.16 min.; ESI-MS m/z (Relative
intensities) (+ve mode) 564.1 (M+H)+, (90%), 585.9 (M+Na)+, (100%).
13. (a) Corey, E. J.; Schmidt, G. Tetrahedron Lett. 1979, 20, 399–402; (b) Martin, T.;
Soler, M. A.; Betancort, J. M.; Martin, V. S. J. Org. Chem. 1997, 62, 1570–1571; (c)
Harding, K. E.; May, L. M.; Dick, K. F. J. Org. Chem. 1975, 40, 1664–1665; (d)
Smith, A. B.; Leenay, T. L. Tetrahedron Lett. 1988, 29, 49–52.
14. (a) Parikh, J. R.; Doering, W. van E. J. Am. Chem. Soc. 1967, 89, 5505–5507; (b)
Panek, J. S.; Masse, C. E. J. Org. Chem. 1997, 62, 8290–8291; (c) Kjell, D. P.;
Slattery, B. J.; Semo, M. J. J. Org. Chem. 1999, 64, 5722–5724.
15. Whitmore, F. C.; George, R. S. J. Am. Chem. Soc. 1942, 64, 1239–1242.
16. (a) Dal Piaz, V.; Giovannoni, M. P.; Castellena, M. C.; Vergelli, C. Il Farmaco 2002,
57, 89–96; (b) Bakthvatchalam, R.; Gilligan, P. J.; U.S. Patent 6271380, 2001;
Chem. Abstr. 2000, 133, 74025y.
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18. General procedure for preparation of aryl carboxamides (15a–e): To the stirring
solution of acid (1.5 equiv) in DCM, EDCI, HCl (2.4 equiv) and 4-N,N-
dimethylamino pyridine (1 equiv) were added simultaneously under
nitrogen atmosphere at 26 °C. The amine (14a) (1 equiv) was added portion-