S. Sathapornvajana, T. Vilaivan / Tetrahedron 63 (2007) 10253–10259
10257
30.4 [CH2(3)], 46.3 (CH2N), 60.0 (CHN), 60.7 (OCH2CH3),
(br), 1669 (s), 1591 (m), 1547 (m), 1420 (w), 1318 (w),
1184 (m), 1137 (m); Anal. Calcd for C13H13Cl2F3N2O4: C,
40.12; H, 3.37; N, 7.20. Found: C, 40.18; H, 3.37; N, 7.30%.
1
115.5 (aromatic CH), 117.5 (q, JCF¼296.6 Hz, CF3 TFA),
120.7 (aromatic CH), 124.1 (aromatic CH), 125.6 (aromatic
CH), 127.5 (aromatic CH), 153.4 (aromatic CH), 159.3 (q,
2JCF¼31.1 Hz, CO TFA), 165.9 (CO ester), 168.0 (CO
amide); IR (KBr, nmax, cmꢁ1): 3440 (br), 3129 (br), 1667
(s), 1607 (m), 1561 (m), 1449 (w), 1386 (w), 1276 (m),
1189 (m), 1135 (m); Anal. Calcd for C16H19ClF3N2O6: C,
48.98; H, 4.88; N, 7.14. Found: C, 48.99; H, 4.88; N, 7.12%.
4.2.8. Pyrrolidine-2-carboxylic acid (30-chloro-50-fluoro-
20-hydroxy-phenyl)-amide trifluoroacetate (3k). Brown
solid (0.240 g, 69% two steps); mp 151.9–154.1 ꢀC (dec),
1
[a]2D5 ꢁ44.8 (c 1.0, MeOH); H NMR (400 MHz, DMSO-
d6) d 1.94 [m, 3H, CHaHb(3) and CH2(4)], 2.35 [m, 1H,
CHaHb(3)], 3.25 (m, 2H, CH2N), 4.54 (m, 1H, CHN), 7.16
3
3
4.2.5. Pyrrolidine-2-carboxylic acid (20-hydroxy-40-tri-
fluoromethyl-phenyl)-amide trifluoroacetate (3h). White
solid (0.186 g, 82% two steps); mp 205.5–207.7 ꢀC (dec),
[d, JHF¼8.0 Hz, 1H, Ar-H(4)], 7.67 (d, JHF¼10.0 Hz,
1H, Ar-H(6)], 8.70 (br, pyrrolidine NH), 9.88 (amide NH),
10.23 (OH); 13C NMR (100 MHz, DMSO-d6) d 24.0
[CH2(4)], 30.3 [CH2(3)], 46.3 (CH2N), 60.0 (CHN), 109.0
1
[a]2D5 ꢁ35.4 (c 1.0, MeOH); H NMR (400 MHz, DMSO-
2
2
d6) d 1.92 [m, 3H, CHaHb(3) and CH2(4)], 2.38 [m, 1H,
CHaHb(3)], 3.27 (m, 2H, CH2N), 4.55 (m, 1H, CHN), 7.16
[d, J¼8.0 Hz, 1H, Ar-H(5)], 7.18 [s,1H, Ar-H(3)], 8.11 [d,
J¼8.0 Hz, 1H, Ar-H(6)], 9.00 (br, pyrrolidine NH), 10.10
(amide NH), 11.08 (OH); 13C NMR (100 MHz, DMSO-d6)
d 24.1 [CH2(4)], 30.4 [CH2(3)], 46.4 (CH2N), 60.1 (CHN),
111.8 (aromatic CH), 116.2 (aromatic CH), 117.3 (q,
1JCF¼129.1 Hz, CF3 TFA), 122.5 (aromatic CH), 124.5 (q,
(d, JCF¼27.2 Hz, aromatic CH), 112.6 (d, JCF¼26.1 Hz,
1
aromatic CH), 117.5 (q, JCF¼297.0 Hz, CF3 TFA), 122.2
3
3
(d, JCF¼12.9 Hz, aromatic CH), 128.9 (d, JCF¼12.3 Hz,
1
aromatic CH), 141.7 (aromatic CH), 154.8 (d, JCF
¼
2
235.6 Hz, aromatic CH), 159.0 (q, JCF¼33.7 Hz, CO
TFA), 168.5 (CO amide); IR (KBr, nmax, cmꢁ1): 3446 (br),
3262 (br), 1672 (s), 1609 (m), 1552 (m), 1480 (m), 1446
(m), 1322 (w), 1198 (s), 1134 (m); Anal. Calcd for
C13H13ClF4N2O4: C, 41.89; H, 3.52; N, 7.52. Found: C,
41.90; H, 3.57; N, 7.52%.
2
1JCF¼270.0 Hz, CF3), 125.4 (q, JCF¼31.7 Hz, aromatic
CH), 129.6 (aromatic CH), 148.6 (aromatic CH), 158.8 (q,
2JCF¼31.1 Hz, CO TFA), 168.3 (CO amide); IR (KBr,
nmax, cmꢁ1): 3435 (br), 3160 (br), 1670 (s), 1618 (m),
1556 (m), 1428 (m), 1343 (m), 1191 (m), 1122 (m); Anal.
Calcd for C14H14F6N2O4: C, 43.31; H, 3.63; N, 7.22. Found:
C, 43.52; H, 3.68; N, 7.14%.
4.2.9. Pyrrolidine-2-carboxylic acid (30,50-difluoro-20-
hydroxy-phenyl)-amide trifluoroacetate (3l). White solid
(0.2195 g, 67% two steps); mp 166.7–168.8 ꢀC (dec), [a]D25
ꢁ40.3 (c 1.0, MeOH); 1H NMR (400 MHz, DMSO-d6)
d 1.91 [m, 3H, CHaHb(3) and CH2(4)], 2.36 [m, 1H,
CHaHb(3)], 3.25 (m, 2H, CH2N), 4.55 (m, 1H, CHN), 7.04
[m, 1H, Ar-H(4)], 7.54 (m, 1H, Ar-H(6)], 8.80 and 9.30
(br, pyrrolidine NH), 10.21 (2H, amide NH and OH); 13C
NMR (100 MHz, DMSO-d6) d 24.0 [CH2(4)], 30.4
[CH2(3)], 46.4 (CH2N), 60.0 (CHN), 100.4 (dd,
2JCF¼27.0, 23.5 Hz, aromatic CH), 104.9 (d, 2JCF¼27.3 Hz,
4.2.6. Pyrrolidine-2-carboxylic acid (30-chloro-20-
hydroxy-phenyl)-amide trifluoroacetate (3i). White solid
(0.238 g, 96% two steps); mp 110.3–113.2 ꢀC (dec), [a]D25
ꢁ39.3 (c 1.0, MeOH); 1H NMR (400 MHz, DMSO-d6)
d 1.94 [m, 3H, CHaHb(3) and CH2(4)], 2.36 [m, 1H,
CHaHb(3)], 3.24 (m, 2H, CH2N), 4.49 (m, 1H, CHN), 6.85
[t, J¼8.0 Hz, 1H, Ar-H(5)], 7.19 [d, J¼8.0 Hz, 1H, Ar-
H(4)], 7.60 [d, J¼8.0 Hz, 1H, Ar-H(6)], 8.90 and 9.40 (br,
pyrrolidine NH), 9.80 (amide NH), 10.08 (OH); 13C NMR
(100 MHz, DMSO-d6) d 29.1 [CH2(4)], 35.2 [CH2(3)],
1
aromatic CH), 117.7 (q, JCF¼298.0 Hz, CF3 TFA), 128.8
3
(aromatic CH), 132.8 (d, JCF¼16.5 Hz, aromatic CH),
2
3
151.5 (dd, JCF¼237.9, JCF¼14.9 Hz, aromatic CH),
154.2 (dd, 1JCF¼233.4, 3JCF¼12.3 Hz, aromatic CH), 158.6
1
2
51.4 (CH2N), 65.0 (CHN), 117.9 (q, JCF¼298.2 Hz, CF3
(q, JCF¼30.8 Hz, CO TFA), 168.3 (CO amide); IR (KBr,
TFA), 125.5 (aromatic CH), 126.7 (aromatic CH), 128.1 (ar-
omatic CH), 131.7 (aromatic CH), 132.7 (aromatic CH),
nmax, cmꢁ1): 3154 (br), 1671 (s), 1625 (m), 1562 (m),
1500 (w), 1463 (m), 1379 (w), 1237 (m), 1184 (s), 1135
(m); Anal. Calcd for C13H13ClF5N2O4: C, 43.83; H, 3.68;
N, 7.86. Found: C, 44.03; H, 3.99; N, 7.94%.
2
160.7 (aromatic CH), 163.5 (q, JCF¼30.7 Hz, CO TFA),
173.2 (CO amide); IR (KBr, nmax, cmꢁ1): 3442 (br), 1680
(s), 1602 (w), 1546 (w), 1459 (w), 1201 (m), 1139 (m);
Anal. Calcd for C13H14ClF3N2O4: C, 44.02; H, 3.98; N,
7.90. Found: C, 44.03; H, 4.00; N, 7.94%.
4.2.10. Pyrrolidine-2-carboxylic acid (50-chloro-20-
methoxy-phenyl)-amide trifluoroacetate (4a). White solid
(0.243 g, 82% two steps); mp 185.5–186.9 ꢀC, [a]D25 ꢁ28.2
1
4.2.7. Pyrrolidine-2-carboxylic acid (30,50-dichloro-20-
hydroxy-phenyl)-amide trifluoroacetate (3j). White solid
(0.259 g, 78% two steps); mp 150.2–152.3 ꢀC (dec), [a]D25
ꢁ34.6 (c 1.0, MeOH); 1H NMR (400 MHz, DMSO-d6)
d 1.89 [m, 2H, CH2(4)], 1.97 [m, 1H, CHaHb(3)], 2.32 [m,
1H, CHaHb(3)], 3.23 (m, 2H, CH2N), 4.49 (m, 1H, CHN),
7.34 [s, 1H, Ar-H(4)], 7.82 [s, 1H, Ar-H(6)], 9.30 (br, pyrro-
lidine NH and amide NH), 10.20 (OH); 13C NMR
(100 MHz, DMSO-d6) d 24.0 [CH2(4)], 30.2 [CH2(3)],
(c 1.0, MeOH); H NMR (400 MHz, CDCl3) d 1.92 [m,
3H, CHaHb(3) and CH2(4)], 2.34 [m, 1H, CHaHb(3)], 3.26
(m, 2H, CH2N), 3.83 (s, 3H, OCH3), 4.55 (m, 1H, CHN),
7.08 [d, J¼8.8 Hz, 1H, Ar-H(3)], 7.17 [dd, J¼8.8, 2.4 Hz,
1H, Ar-H(4)], 7.99 [d, J¼2.4 Hz, 1H, Ar-H(6)], 9.10 (br,
pyrrolidine NH), 10.09 (amide NH); 13C NMR (100 MHz,
CDCl3) d 24.0 [CH2(4)], 30.4 [CH2(3)], 46.3 (CH2N), 56.6
(OCH3), 60.0 (CHN), 113.3 (aromatic CH), 117.6 (q,
1JCF¼296.6 Hz, CF3 TFA), 122.0 (aromatic CH), 124.2
(aromatic CH), 125.1 (aromatic CH), 127.9 (aromatic
1
46.4 (CH2N), 60.0 (CHN), 117.6 (q, JCF¼298.1 Hz, CF3
2
TFA), 122.1 (aromatic CH), 122.5 (aromatic CH), 123.3 (ar-
omatic CH), 125.5 (aromatic CH), 128.9 (aromatic CH),
CH), 149.2 (aromatic CH), 158.9 (q, JCF¼27.3 Hz, CO
TFA), 168.2 (CO amide); IR (KBr, nmax, cmꢁ1): 3275
(m), 2991 (w), 1673 (s), 1601 (m), 1545 (s), 1485 (m),
1425 (w), 1318 (w), 1201 (s), 1131(s); Anal. Calcd for
2
144.5 (aromatic CH), 158.8 (q, JCF¼31.1 Hz, CO TFA),
168.5 (CO amide); IR (KBr, nmax, cmꢁ1): 3434 (br), 3172