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J. Parcerisa et al. / Tetrahedron 64 (2008) 500e507
water. The mixture was extracted with 3ꢂ20 mL of ether. The
organic layer was washed with 2ꢂ20 mL of distilled water,
dried over anhydrous sodium sulfate, and filtered off. The sol-
vent was removed by evaporation under vacuum. The crude of
reaction was dissolved in 5 mL of CH2Cl2 and loaded into
a 3ꢂ30 cm column of chromatography packed with silica
gel. An increasing polarity elution gradient of ethyl acetate/
methanol was used.
for C20H26N2O5: C, 64.15; H, 7.00; N, 7.48%. Found: C,
64.43; H, 7.34; N, 7.20%.
4.3.4. 3-(2-Hydroxy-2-(4-nitrophenyl)ethyl)-2-[N-(tert-
butoxycarbonyl)]aminopyridine (2d)
Thegeneral procedurewas followed using 0.175 g (1.2 mmol)
of 4-nitrobenzaldehyde to give 0.515 g (1.46 mmol, 75%) of pure
3-(2-hydroxy-2-(4-nitrophenyl)ethyl)-2-[N-(tert-butoxycarbo-
nyl)]aminopyridine. Mp 94e95 ꢀC (ethyl acetate). IR (NaCl) n
(cmꢁ1): 3276 (OH), 2975 (NH), 1728 (C]O), 1454, 1247 (Ce
O), 1157 (CeO). 1H NMR (CDCl3, 200 MHz) d (ppm): 1.33 (s,
9H, CH3), 2.92 (m, 2H, CH2e), 4.92 (br s, 1H, OH), 5.02 (m, 1H,
CHeOe), 6.99 (m, 1H), 7.23 (m, 1H), 7.45 (d, J¼7.0 Hz, 2H),
4.3.1. 2-tert-Butoxycarbonylamino-3-(2-hydroxy-2-
(4-pyridyl)ethyl)pyridine (2a)
The general procedure was followed using 0.23 g
(2.1 mmol) of 4-pyridinecarbaldehyde to give 0.392 g
(1.24 mmol, 87%) of pure 3-(2-hydroxy-2-(4-pyridyl)ethyl)-
2-[N-(tert-butoxy carbonyl)]aminopyridine 2a as a white solid.
Mp 45e47 ꢀC (hexane/ethyl acetate). IR (KBr) n cmꢁ1: 3220
(OH), 1726 (C]O), 1504 (C]C), 1238 (AreO), 1156 (CeO).
1H NMR (CDCl3, 200 MHz) d (ppm): 1.49 (s, 9H, CH3e), 2.98
(m, 2H, CH2), 3.05 (m, 1H, eOH), 5.02 (m, 1H,
CHeOH), 7.08 (m, 1H), 7.91 (d, J¼9.20 Hz, 2H), 7.42 (d,
J¼9.20 Hz, 1H), 8.25 (m, J¼3.8 Hz, 1H), 8.40 (d, J¼9.2 Hz,
2H). 13C NMR (CDCl3, 50.3 MHz) d (ppm): 28.3 (CH3), 40.8
(CH2), 73.1 (CH, CHeOe), 80.6 (C, t-bu), 119.9, 120.8, 125.7,
139.8, 146.6, 149.1, 131.2, 152.9, 153.7. Anal. Calcd for
C17H21N3O3: C, 64.74; H, 6.71; N, 13.32%. Found: C, 64.67;
H, 6.43; N, 13.71%.
8.02 (d, J¼7.0 Hz, 2H), 8.20 (m, 1H), 8.21 (br s, 1H, NH). 13
C
NMR (CDCl3, 50.3 MHz) d (ppm): 28.0 (CH3), 40.9 (CH2),
73.3 (CH, CHeOe), 80.1 (C, t-bu), 120.2, 123.3, 126.3,
130.1, 140.2, 146.3, 148.0, 149.9, 151.8, 153.4. Anal. Calcd
for C18H21N3O5: C, 60.16; H, 5.89; N, 11.70%. Found: C,
60.52; H, 5.52; N, 11.54%.
4.3.5. 3-(2-Hydroxypentyl)-2-[N-(tert-butoxycarbonyl)]
aminopyridine (2e)
The general procedure was followed using 0.16 g
(2.22 mmol) of butyraldehyde to give 0.249 g (0.9 mmol,
62%) of colorless oil. IR (KBr) n (cmꢁ1): 3275 (OeH),
1
4.3.2. 3-(2-Hydroxy-2-(thiophen-2-yl)ethyl)-2-[N-(tert-
butoxycarbonyl)]aminopyridine (2b)
2958 (NH), 1736 (C]O), 1246 (AreOe), 1163 (CeO). H
NMR (CDCl3, 200 MHz) d (ppm): 0.95 (m, 3H, CH3e),
0.98 (m, 2H, CH2eCH3), 1.48 (s, 9H, t-bu), 1.52 (m, 2H),
2.20 (br s, 1H, OH), 2.72 (m, 2H), 3.96 (m, 1H, CHeOH),
7.01 (dd, J1¼7.4 Hz, J2¼4.6 Hz, 1H), 7.45 (dd, J1¼7.4 Hz,
J2¼1.4 Hz, 1H), 8.15 (s, 1H, NeH), 8.29 (dd, J1¼4.6 Hz, J2¼
1.4 Hz, 1H). 13C NMR (CDCl3, 50.3 MHz) d (ppm): 14.0
(CH3), 18.8 (CH2), 28.3 (CH3, t-bu), 38.8 (CH2), 39.7 (CH2),
72.4 (CH, CHeO), 80.2 (C, t-bu), 119.8, 126.9, 139.5, 146.2,
150.5, 152.9. Anal. Calcd for C15H24N2O3: C, 64.26; H, 8.63;
N, 9.99%. Found: C, 64.58; H, 8.91; N, 9.68%.
The general procedure was followed using 0.245 g
(2.19 mmol) of freshly distilled 2-thiophenecarboxaldehyde
to give 0.376 g (1.17 mmol, 82%) of 2b as a yellow solid (hex-
ane/ethyl acetate 30:70, v/v). Mp 112e113 ꢀC (ethyl acetate).
IR (KBr) n (cmꢁ1): 3209 (OH), 1730 (C]O), 1159 (CeOe).
1H NMR (CDCl3, 200 MHz) d (ppm): 1.48 (s, 9H, CH3e),
3.07 (d, J¼6.2 Hz, CH2e), 4.36 (br s, 1H, OH), 5.22 (t, J¼
6.2 Hz, 1H, CHeOH), 6.92 (m, 3H), 7.20 (m, 1H), 7.40 (d,
J¼7.4 Hz, 1H), 8.20 (m, 1H). 13C NMR (CDCl3, 50.3 MHz)
d (ppm): 28.3 (CH3), 41.4 (CH2), 70.7 (CH, CHeOH), 80.6
(C, t-bu), 120.2, 123.3, 124.3, 126.2, 126.6, 139.8, 146.6,
148.2, 150.4, 153.2. Anal. Calcd for C16H20N2O3S: C, 59.98;
H, 6.29; N, 8.74%. Found: C, 59.67; H, 6.12; N, 8.43%.
4.3.6. 3-[2-Hydroxy-2-(4-methoxyphenyl)]ethyl-2-[N-(tert-
butoxycarbonyl)]aminopyridine (2f)
Starting from 0.3 g (1.44 mmol) of 2-tert-butoxycarbonyl-
3-methylpyridine 1 dissolved in 5 mL of dry THF and follow-
ing the above reported method was obtained the carbinol 2f
as a yellow solid (82% yield). Mp 110e111 ꢀC (hexane/ethyl
acetate). IR (KBr) n (cmꢁ1): 3282 (OeH), 3055 (NH), 1723
(C]O), 1244 (AreOe), 1158 (CeO). 1H NMR (CDCl3,
300 MHz) d (ppm): 1.64 (s, 9H, CH3e), 3.12 (d, J¼6 Hz,
2H, CH2e), 3.96 (s, 3H, CH3Oe), 5.13 (t, J¼6 Hz, 1H,
CHeO), 7.02 (d, J¼8 Hz, 2H), 7.10 (t, J¼6 Hz, 1H), 7.40
(d, J¼8 Hz, 2H), 7.45 (d, J¼8 Hz, 1H, H-4), 8.25 (s, 1H),
8.42 (s, 2H, NH, OH). 13C NMR (CDCl3, 50.3 MHz) d (ppm):
28.2 (CH3), 41.2 (CH2), 55.2 (CH3), 74.6 (CH, CHeO), 80.4
(C, t-bu), 114.0, 119.9, 127.3, 135.9, 139.5, 139.7, 146.7,
148.2, 152.0, 158.2. Anal. Calcd for C19H24N2O4: C, 66.26;
H, 7.02; N, 8.13%. Found: C, 66.13; H, 7.38; N, 7.89%.
4.3.3. 3-(2-Hydroxy-2-(2,4-dimethoxyphenyl)ethyl)-2-
[N-(tert-butoxycarbonyl)]aminopyridine (2c)
The general procedure was followed using 0.287 g
(1.7 mmol) of 2,4-dimethoxybenzaldehyde to give 0.43 g
(1.09 mmol, 78%) of 2c as a white solid powder. IR (KBr) n
(cmꢁ1): 3381 (OeH), 2970 (NH), 1734 (C]O), 1256 (Are
Oe), 1253 (CeO). 1H NMR (CDCl3, 200 MHz) d (ppm): 1.39
(s, 9H, CH3e), 2.68 (m, 2H, CH2e), 3.64 (s, 3H, CH3eOe),
3.69 (s, 3H, CH3Oe), 5.01 (m, 1H, CHeOH), 6.27 (s, 1H),
6.31 (m, 1H), 6.78 (m, 1H), 7.11 (m, 1H), 7.16 (m, 1H),
8.10 (m, 1H), 8.38 (s, 1H, NeH). 13C NMR (CDCl3,
50.3 MHz) d (ppm): 28.3 (CH3), 31.0 (CH3), 39.4 (CH3),
55.2 (CH2), 69.5, 80.2, 98.1, 103.9, 119.3, 124.6, 125.9,
126.6, 136.7, 146.2, 150.4, 152.5, 156.4, 159.7. Anal. Calcd