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R. Patil et al. / Tetrahedron Letters 47 (2006) 3941–3944
phy (1:9 ethyl acetate/hexane) to give 3.0 g (55%) of 5 as a
(DMSO-d6) d 7.91 (d, J = 8.4 Hz, 1H, ArH), 7.28 (d,
J = 1.8 Hz, 1H, ArH), 7.18–7.09 (m, 3H, ArH), 6.99–6.93
(m, 2H, ArH), 5.38 (s, 1H, OH), 4.10 (d, J = 9.6 Hz, 1H,
–CH2), 3.81 (d, J = 9.9 Hz, 1H, –CH2), 3.69 (s, 3H,
–NCH3), 1.42 (s, 3H, –CH3); MS (ESI+) m/z 419
yellow oil, which was recrystallized from DCM to furnish
white colored crystals. Mp 128–129 ꢁC. 1H NMR
(300 MHz, DMSO-d6) d 10.57 (br s, 1H, –NH), 8.56 (s,
1H, ArH), 8.31 (d, J = 8.7 Hz, 1H, ArH), 8.10 (d,
J = 8.7 Hz, 1H, ArH), 7.11–7.05 (m, 2H, ArH), 6.95–
6.91 (m, 2H, ArH), 6.26 (br s, 1H, OH), 4.20 (d,
J = 9.6 Hz, 1H, –CH2), 3.96 (d, J = 9.6 Hz, 1H, –CH2),
1.43 (s, 3H, –CH3). MS (ESIꢁ) m/z 381 (MꢁH)ꢁ.
1
(M+Na)+. 9: Mp 96–97 ꢁC H NMR (300 MHz, CDCl3-
d6) d 9.09 (s, 1H, –NH), 8.09 (d, J = 2.1 Hz, 1H, ArH),
7.98 (dd, J = 2.1, 1.8 Hz, 1H, ArH), 7.80 (d, J = 8.4 Hz,
1H, ArH), 7.00–6.92 (m, 2H, ArH), 6.87–6.77 (m, 2H,
ArH), 4.27 (d, J = 9.6 Hz, 1H, –CH2), 4.11 (d,
J = 10.2 Hz, 1H, –CH2), 3.49 (s, 3H, –OCH3), 1.53 (s,
3H, –CH3); MS (ES+) m/z 419 (M+Na)+. 10: Mp 88–
8. (2S)-2-(tert-Butyldimethylsilanyloxy)-N-(4-cyano-3-triflu-
oromethylphenyl)-3-(4-fluorophenoxy)-2-methylpropion-
amide. To a solution of compound 5 (4.00 g, 10.46 mmol)
in dichloromethane (75 mL) was added tert-butyldimeth-
ylsilyl trifluoromethane sulfonate (3.32 g, 12.56 mmol),
and 2,6-lutidine (2.24 g, 20.93 mmol) at 0 ꢁC. The mixture
was stirred at ambient temperature overnight, and diluted
with water. The water layer was extracted with ethyl
acetate, the combined organic layers were dried with
anhydrous Na2SO4, and the solvents were evaporated
under reduced pressure. The resulting crude residue was
purified by flash column chromatography (5:95 ethyl
acetate/hexane) to afford 3.85 g (99%) of 6 as a colorless
oil. (Recovered starting material yield 1.00 g, 25%.) 1H
NMR (300 MHz, DMSO-d6) d 9.76 (s, 1H, –NH), 8.32 (s,
1H, ArH), 8.16 (d, J = 8.4 Hz, 1H, ArH), 8.08 (d,
J = 8.4 Hz, 1H, ArH), 7.14–7.08 (m, 2H, ArH), 6.97–
6.92 (m, 2H, ArH), 4.26 (d, J = 10.2 Hz, 1H, –CH2), 4.11
(d, J = 10.2 Hz, 1H, –CH2), 1.55 (s, 3H, –CH3), 0.91 (s,
9H, 3 · –CH3), 0.14 (d, J = 7.8 Hz, 6H, 2 · –CH3). MS
(ESI+) m/z 519 (M+Na)+.
89 ꢁC 1H NMR (300 MHz, DMSO-d6)
d 8.37 (q,
J = 4.5 Hz, 1H, –NH), 8.09 (d, J = 8.4 Hz, 1H, ArH),
7.52 (d, J = 2.4 Hz, 1H, ArH), 7.39 (dd, J = 2.4, 2.4 Hz,
1H, ArH), 7.15–7.06 (m, 2H, ArH), 7.00–6.91 (m, 2H,
ArH), 4.31 (q, J = 10.8 Hz, 2H, –CH2), 2.66 (d,
J = 4.5 Hz, 3H, –NHCH3), 1.60 (s, 3H, –CH3); MS
(ESI+) m/z 419 (M+Na)+.
11. To a solution of 7 (0.063 g, 0.123 mmol) in anhydrous THF
(10 mL) was added TBAF 1 M solution in THF (0.064 g,
0.247 mmol) at 0 ꢁC. The mixture was stirred at room
temperature for 1 h, diluted with ethyl acetate, and
extracted with water. The organic layer was dried over
anhydrous Na2SO4, and the solvent was removed under
reduced pressure. The crude residue was dissolved in DCM,
and evaporated to give compound 10 (0.027 g, 55%).
12. Kohn, W.; Sham, L. Phys. Rev. A 1965, 140, 1133–
1138.
13. Becke, A. D. J. Chem. Phys. 1993, 98, 5648–5652.
14. Hariharan, P. C.; Pople, J. A. Theoret. Chim. Acta 1973,
28, 213–222.
15. Sychrovsky, V.; Gra¨fenstein, J.; Cremer, D. J. Chem.
Phys. 2000, 113, 3530–3547.
9. Hayat, S.; Rahman, A.-U.; Iqbal, C. M.; Khan, K. M.;
Schumann, W.; Bayer, E. Tetrahedron 2001, 57, 9951–
9957.
10. To a stirred solution of compound 6 (0.946 g, 1.94 mmol)
in anhydrous acetonitrile (20 mL) was added CsF-Celite
(0.442 g, 2.91 mmol) and methyl iodide (0.551 g,
3.88 mmol). The mixture was heated for 5 h, cooled to
room temperature, and concentrated under reduced
pressure. The residue was dissolved in ethyl acetate,
filtered, and the precipitate was washed with ethyl acetate.
The combined filtrates were evaporated under reduced
pressure, and the crude residue was purified by flash
column chromatography (1:9 to 6:4 ethyl acetate/hexane)
afforded compounds 5 (0.149 g, 22%), 7 (0.144 g, 16%), 8
(0.070 g, 10%), 9 (0.077 g, 11%), and 10 (0.259 g, 37%).
(Recovered starting material yield 0.087 g, 9%.) Data for
16. Farrugia, L. J. J. Appl. Cryst. 1997, 30, 565.
17. X-ray crystal structure data were collected to a resolution
˚
of approximately 0.8 A on a Bruker Proteum CCD
detector mounted on a Nonius FR591 rotating-anode
˚
generator using a copper target (k = 1.54178 A) (Bruker
AXS, Inc., Madison, WI). Raw data were integrated using
SAINT and corrected for absorption using SADABS.
Direct-methods structure solution and refinement were
performed using the SHELX programs. Anisotropic
ADPs were refined for all heavy atoms, resulting in the
final refinement statistics of R1 = 0.025 for 3015 reflec-
tions with Fo > 4r(Fo), wR2 = 0.068 and S (goodness-
of-fit) = 1.046 for 3071 reflections and 253 refined para-
meters. Supplementary data in the form of CIFs have been
deposited with the Cambridge Crystallographic Data
Center (CCDC 286917). Copies of the data can be
obtained, free of charge, on application to CCDC, 12
Union Road, Cambridge CB2 1EZ, UK [Fax: +44(0)-
1223-336033 or e-mail: deposit@ccdc.cam.ac.uk].
1
7: H NMR (300 MHz, DMSO-d6) d 8.24 (d, J = 8.1 Hz,
1H, ArH), 7.91 (s, 1H, ArH), 7.82 (d, J = 8.1 Hz, 1H,
ArH), 7.18–7.12 (m, 2H, ArH), 7.00–6.96 (m, 2H, ArH),
4.25 (d, J = 9.9 Hz, 1H, –CH2), 4.01 (d, J = 9.9 Hz, 1H,
–CH2), 3.50 (s, 3H, –NCH3), 1.60 (s, 3H, –CH3), 0.79 (s,
9H, 3 · –CH3), 0.02 (d, J = 4.8 Hz, 6H, 2 · –CH3); MS
(ESI+) m/z 533 (M+Na)+. 8: Mp 85–86 ꢁC 1H NMR