5908
K. D. James, N. N. Ekwuribe / Tetrahedron 58 (2002) 5905±5908
2114.2. IR: 3065, 1719. UV: lmax 251; HRMS-FAB (m/z):
Calcd for C10H11FO3S, 230.0413; found 230.0417.
4.1.6. (2S)-N-[4-Cyano-3-(tri¯uoromethyl)phenyl]-3-[(4-
¯uorophenyl)sulfonyl]-2-hydroxy-2-methylpropanamide.
ee q 99%; Anal. Calcd for C18H14F4N2O4S: C, 50.23; H,
3.28; N, 6.51. Found: C, 50.38; H, 3.41; N, 6.46.
4.1.4. (2R)-N-[4-Cyano-3-(tri¯uoromethyl)phenyl]-3-[(4-
¯uorophenyl)thio]-2-hydroxy-2-methylpropanamide (7).
The hydroxyacid 6 (1.89 g; 8.22 mmol) and 4-amino-2-
tri¯uoromethylbenzonitrile (2.05 g; 11.0 mmol) were dis-
solved in dry DMA (15 mL) under inert atmosphere. After
the solution had been cooled to 2108C, thionyl chloride
(0.75 mL; 10 mmol) was added slowly. The reaction
mixture was stirred for 15 min at 2108C, and then the ice
bath was removed. After stirring overnight at room tempera-
ture, the reaction mixture was diluted with CH2Cl2 and was
extracted one time with satd NaHCO3. The organic layer
was dried with MgSO4 and concentrated. The product was
puri®ed by silica gel chromatography (6% ethyl acetate in
Acknowledgements
We wish to thank T. Ribeiro of Duke University and R.
Stringham of Chiral Technologies for their assistance in
the analyses of some of these compounds.
References
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CH2Cl2). Yield 1.38 g (42%); H NMR (300 MHz, CDCl3,
d): 8.98 (s, 1H), 7.91 (s, 1H), 7.74 (m, 2H), 7.39 (dd, J8.9,
5.1 Hz, 2H), 6.88 (dd, J8.9, 8.5 Hz, 2H), 3.75 (d, J
14.1 Hz, 1H), 3.54 (s, 1H), 3.10 (d, J14.1 Hz, 1H), 1.53
(s, 3H); 13C NMR (75.4 MHz, CDCl3, d): 172.8, 161.8 (d,
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2
1JFC248.7 Hz), 140.9, 135.2, 133.4 (q, JFC33.3 Hz),
3
4
133.2 (d, JFC8.0 Hz), 128.4 (d, JFC3.7 Hz), 121.6 (q,
3
1JFC273.9 Hz), 121.3, 116.8 (q, JFC4.7 Hz), 115.7 (d,
2JFC21.9 Hz), 115.1, 103.8, 75.0, 45.3, 25.6; 19F NM R
(282.3 MHz, CDCl3, d): 262.7, 2113.2. IR: 3357, 3095,
2981, 2232, 1685; HRMS-FAB (m/z): Calcd for
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7. James, K. D.; Ekwuribe, N. Patent pending.
8. James, K. D.; Ekwuribe, N. Synthesis 2002, 850±852.
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¯uorophenyl)sulfonyl]-2-hydroxy-2-methylpropanamide
(2). To a solution of the sul®de 7 (1.27 g; 3.19 mmol) in
CH2Cl2 (43 mL) was added mCPBA (1.65 g; 9.57 mmol).
After stirring overnight at room temperature, the reaction
mixture was diluted with ethyl acetate and extracted with
Na2SO3 and NaHCO3 (2£). The organic layer was dried
with MgSO4 and concentrated. After puri®cation by silica
gel chromatography using a step gradient of ethyl acetate in
CHCl3, the product was obtained as white crystals from
benzene/petroleum ether. Yield 1.29 g (94%); ee q 99%;
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1
mp 1788C; MS (FAB1) 431 (M11); H NMR (300 MHz,
CDCl3, d): 9.16 (s, 1H), 8.00 (d, J1.5 Hz, 1H), 7.88±7.93
(m, 2H), 7.79±7.80 (m, 2H), 7.14±7.20 (m, 2H), 5.02 (s,
1H), 4.00 (d, J14.5 Hz, 1H), 3.51 (d, J14.5 Hz, 1H), 1.61
(s, 3H); 13C NMR (75.4 MHz, CDCl3, d): 171.4, 166.0
18. James, K. D.; Ekwuribe, N. Patent pending.
19. Terashima, S.; Jew, S.-s. Tetrahedron Lett. 1977, 1005±1008.
20. Mukherjee, A.; Kirkovsky, L.; Yao, X. T.; Yates, R. C.;
Miller, D. D.; Dalton, J. T. Xenobiotica 1996, 26, 117±122.
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D. D. J. Med. Chem. 2000, 43, 581±590.
1
2
(d, JFC256.7 Hz), 141.0, 135.7, 135.0, 133.9 (q, JFC
3
1
32.4 Hz), 130.8 (d, JFC9.7 Hz), 121.9 (q, JFC
2
272.0 Hz), 121.8, 117.2, 116.8 (d, JFC22.7 Hz), 115.3,
104.8, 74.4, 61.8, 27.8; 19F NMR (282.3 MHz, CDCl3, d):
262.7, 2101.6. IR: 3449, 3333, 3104, 2984, 2933, 2231,
1697, 1587, 1517. UV: lmax 214, 271. [a]2828 (c 1.0,
MeOH). Anal. Calcd for C18H14F4N2O4S: C, 50.23; H,
3.28; N, 6.51. Found: C, 50.01; H, 3.26; N, 6.23.
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