9376
C.I.C. Esteves et al. / Tetrahedron 65 (2009) 9373–9377
The filtrate was evaporated in a rotary evaporator. The resulting
solid was purified by recrystallization from methanol and diethyl
ether or column chromatography, using mixtures of ethyl acetate
and light petroleum of increasing polarity.
(0.577 g, 1.15 mmol, 91%). Mp¼117.0–118.9 ꢁC. IR (KBr, 1%):
¼3369,
n
3208, 3068, 2979, 2932, 1764, 1747, 1727, 1695, 1607, 1572, 1556,
1520, 1461, 1417, 1392, 1368, 1344, 1262, 1222, 1158, 1062, 982, 944,
912, 892, 853, 820, 805, 780, 752, 732, 700, 665, 515 cmꢀ1. 1H NMR
(400 MHz, CDCl3):
3.02–3.28 (m, 2H,
4.0 Hz, 1H, -H), 5.16–5.24 (m, 2H, CH2), 5.89 (d, J 8.4 Hz, 1H, NH
d
¼1.42–1.48 (m, 12H, C(CH3)3 and OCH2CH3),
4.2.1. N-tert-Butyloxycarbonyl (benzothiazol-2-yl) asparagine benzyl
b-CH2), 4.08 (q, J 6.8 Hz, 2H, OCH2CH3), 4.75 (t, J
ester (3a). The product was isolated as
a
colourless solid
a
(0.512 g, 1.12 mmol, 90%). Mp¼124.4–124.6 ꢁC. IR (KBr, 1%):
n¼3377,
Boc), 7.01 (dd, J 8.8 and 2.4 Hz, 1H, H5), 7.25–7.30 (m, 6H, 5ꢂPh-H
2970, 2931,1758,1729,1698,1627,1600,1552,1519,1444,1422,1391,
1368, 1347, 1299, 1272, 1245, 1212, 1198, 1170, 1158, 1066, 1016, 983,
909, 873, 784, 755, 729, 696, 666 cmꢀ1. 1H NMR (300 MHz, CDCl3):
and H7), 7.62 (d, J 8.8 Hz,1H, H4), 8.55 (br s,1H, NH amide) ppm. 13C
NMR (100.6 MHz, CDCl3):
d
¼14.79 (OCH2CH3), 28.22 (C(CH3)3),
38.28 ( -CH2), 50.10 ( -C), 64.15 (OCH2CH3), 67.57 (CH2), 80.22
b
a
d
¼1.44 (s, 9H, C(CH3)3), 3.18–3.40 (m, 2H,
b
-CH2), 4.80 (t, J 3.9 Hz,1H,
(C(CH3)3), 105.09 (C7), 116.03 (C5), 120.77 (C4), 128.16 (C30 and C50),
128.27 (C40), 128.46 (C20 and C60), 132.45 (C7a), 135.12 (C10), 140.44
(C3a), 155.57 (C]O urethane), 156.42 (C6), 157.08 (C2), 169.03
(C]O amide), 170.94 (C]O ester) ppm. UV–Vis (ethanol, nm): lmax
a
-H), 5.18–5.23 (m, 2H, CH2), 5.64 (d, J 8.4 Hz,1H, NH Boc), 7.22–7.38
(m, 6H, 5ꢂPh-H and NH amide), 7.49 (dt, J 7.2 and 1.2 Hz, 1H, H6),
7.60 (dt, J 7.2 and 1.2 Hz,1H, H5), 7.84–7.89 (m, 2H, H4 and H7) ppm.
13C NMR (75.4 MHz, CDCl3):
d
¼28.22 (C(CH3)3), 38.44 (
b
-CH2), 50.07
(log
3
)¼345 (3.34). MS m/z (ESI, %): 522 (Mþþ23, 100), 500
(
a
-C), 67.64 (CH2), 80.31 (C(CH3)3), 120.04 (C7), 121.59 (C4), 124.51
([MþH]þ, 8). C25H29N3O6S: calcd C 60.10, H 5.85, N 8.41, S 6.42;
(C6), 126.85 (C5), 128.21 (C40), 128.31 (C30 and C50), 128.48 (C20 and
C60), 130.91 (C7a), 135.05 (C10), 145.81 (C3a), 155.53 (C]O ure-
thane), 159.23 (C2), 169.31 (C]O amide), 170.86 (C]O ester) ppm.
found C 60.20, H 5.98, N 8.21, S 6.19.
4.2.5. N-tert-Butyloxycarbonyl (6-fluorobenzothiazol-2-yl) asparagine
benzyl ester (3e). The product was isolated as a colourless solid
(0.282 g, 0.60 mmol, 65%). Mp¼152.2–154.0 ꢁC. IR (KBr, 1%):
UV–Vis (ethanol, nm): lmax (log
3)¼330 (3.22). MS m/z (ESI, %): 478
(Mþþ23, 100), 456 ([MþH]þ, 20). C23H25N3O5S: calcd C 60.64, H
5.53, N 9.22, S 7.04; found C 60.80, H 5.73, N 9.25, S 7.15.
n
¼3370, 3264, 3217, 3069, 2981, 2932, 1755, 1741, 1696, 1609, 1557,
1520, 1461, 1425, 1417, 1391, 1368, 1344, 1318, 1287, 1251, 1222, 1197,
1167, 1153, 1054, 1029, 1020, 990, 979, 916, 851, 826, 808, 780 cmꢀ1
1H NMR (300 MHz, CDCl3):
¼1.41 (s, 9H, C(CH3)3), 3.08–3.31 (m,
2H, -CH2), 4.82 (t, J 3.6 Hz,1H, -H), 5.17–5.26 (m, 2H, CH2), 6.09 (d,
4.2.2. N-tert-Butyloxycarbonyl (6-methylbenzothiazol-2-yl) aspara-
gine benzyl ester (3b). The product was isolated as a colourless solid
(0.523 g, 1.11 mmol, 89%). Mp¼154.9–158.0 ꢁC. IR (KBr, 1%):
.
d
b
a
n
¼3369, 3210, 3066, 2982, 2931, 1755, 1737, 1698, 1607, 1553, 1521,
J 7.5 Hz,1H, NH Boc), 7.08 (dt, J 9.0 and 2.4 Hz,1H, H5), 7.24–7.33 (m,
5H, 5ꢂPh-H), 7.46 (dd, J 7.8 and 2.1 Hz, 1H, H7), 7.65–7.69 (m, 1H,
H4), 9.50 (br s, 1H, NH amide) ppm. 13C NMR (75.4 MHz, CDCl3):
1467, 1455, 1422, 1389, 1368, 1343, 1317, 1273, 1223, 1208, 1155,
1060, 1029, 990, 900, 866, 814, 779, 736, 695, 665 cmꢀ1 1H NMR
(400 MHz, CDCl3):
¼1.42 (s, 9H, C(CH3)3), 2.47 (s, 3H, CH3), 3.03–
3.28 (m, 2H, -CH2), 4.75 (t, J 4.0 Hz, 1H, -H), 5.17–5.25 (m, 2H,
.
d
d
¼28.17 (C(CH3)3), 38.21 (
b-CH2), 50.14 (a-C), 67.64 (CH2), 80.30
b
a
(C(CH3)3), 107.66 (d, J 26.8 Hz, C7),114.74 (d, J 24.5 Hz, C5), 121.44 (d,
J 8.90 Hz, C4), 128.12 (C30 and C50),128.30 (C40), 128.45 (C20 and C60),
132.59 (d, J 10.3 Hz, C7a), 135.00 (C10), 143.80 (C3a), 155.64 (C]O
urethane), 158.27 (C2), 159.56 (d, J 243.8 Hz, C6), 169.32 (C]O
amide), 171.09 (C]O ester) ppm. UV–Vis (ethanol, nm): lmax
CH2), 5.91 (d, J 8.4 Hz, 1H, NH Boc), 7.23 (dd, J 8.0 and 1.4 Hz, H5),
7.25–7.32 (m, 5H, 5ꢂPh-H), 7.60 (d, J 1.4 Hz, H7), 7.63 (d, J 8.0 Hz,
H4), 9.58 (br s, 1H, NH amide) ppm. 13C NMR (100.6 MHz, CDCl3):
d¼21.39 (CH3), 28.21 (C(CH3)3), 38.28 (
b-CH2), 50.05 (a-C), 67.55
(CH2), 80.19 (C(CH3)3), 119.86 (C4), 121.26 (C7), 128.09 (C5), 128.13
(C30 and C50), 128.26 (C40), 128.45 (C20 and C60), 131.51 (C7a), 134.35
(C6), 135.13 (C10), 144.74 (C3a), 155.58 (C]O urethane), 158.37 (C2),
169.21 (C]O amide), 170.95 (C]O ester) ppm. UV–Vis (ethanol,
(log
3
)¼346 (3.52). MS m/z (ESI, %): 496 (Mþþ23,100), 474 ([MþH]þ,
15). C23H24N3O5SF: calcd C 58.34, H 5.11, N 8.87; found C 58.33, H
5.27, N 8.86.
nm): lmax (log
3
)¼326 (3.28). MS m/z (ESI, %): 492 (Mþþ23, 100),
4.2.6. N-tert-Butyloxycarbonyl (6-nitrobenzothiazol-2-yl) asparagine
benzyl ester (3f). The product was isolated as a colourless solid
(0.368 g, 0.74 mmol, 58%). Mp¼114.7–120.5 ꢁC. IR (KBr, 1%):
470 ([MþH]þ, 13). C24H27N3O5S: calcd C 61.39, H 5.80, N 8.95, S
6.83; found C 61.09, H 5.87, N 8.85, S 6.89.
n
¼3377, 2970, 2931, 1758, 1729, 1698, 1627, 1600, 1552, 1519, 1444,
4.2.3. N-tert-Butyloxycarbonyl (6-methoxybenzothiazol-2-yl) aspar-
agine benzyl ester (3c). The product was isolated as a colourless
solid (0.439 g, 0.90 mmol, 89%). Mp¼130.2–134.0 ꢁC. IR (KBr, 1%):
1422, 1552, 1519, 1455, 1444, 1391, 1368, 1347, 1299, 1272, 1245,
1212, 1198, 1158, 1170, 1066, 1016, 983, 909, 873, 784, 755, 729, 696,
666 cmꢀ1. 1H NMR (400 MHz, CDCl3):
d¼1.43 (s, 9H, C(CH3)3), 3.10–
n
¼3367, 2979, 2932, 1754, 1730, 1695, 1606, 1570, 1556, 1521, 1471,
3.27 (m, 2H, b-CH2), 4.78 (br s,1H, a-H), 5.19–5.31 (m, 2H, CH2), 5.68
1439, 1368, 1345, 1264, 1222, 1157, 1061, 1029, 902, 853, 829, 810,
779, 753, 733, 700, 666, 514 cmꢀ1 1H NMR (400 MHz, CDCl3):
-CH2), 3.87 (s, 3H,
-H), 5.17–5.24 (m, 2H, CH2), 5.90 (d, J
(br s, 1H, NH Boc), 7.27–7.33 (m, 6H, 5ꢂPh-H and NH amide), 7.85
(d, J 8.7 Hz, 1H, H4), 8.35 (dd, J 9.0 and 2.4 Hz, 1H, H5), 8.76 (d, J
.
d
¼1.42 (s, 9H, C(CH3)3), 3.03–3.28 (m, 2H,
b
2.4 Hz, 1H, H7) ppm. 13C NMR (100.6 MHz, CDCl3):
(C(CH3)3), 38.74 (b-CH2), 50.31 (a-C), 67.97 (CH2), 80.76 (C(CH3)3),
d
¼28.26
OCH3), 4.76 (t, J 4.0 Hz, 1H,
a
8.4 Hz, 1H, NH Boc), 7.01 (dd, J 8.8 and 2.4 Hz, 1H, H5), 7.25–7.30 (m,
6H, 5ꢂPh-H and H7), 7.63 (d, J 8.8 Hz, 1H, H4), 9.05 (br s, 1H, NH
118.09 (C7), 120.84 (C4), 122.17 (C5), 128.29 (C40), 128.51 (C30 and
C50), 128.56 (C20 and C60), 132.08 (C7a), 134.85 (C10), 144.07 (C3a),
151.97 (C6), 155.74 (C]O urethane), 162.38 (C2), 169.53 (C]O
amide), 170.89 (C]O ester) ppm. UV–Vis (ethanol, nm): lmax
amide) ppm. 13C NMR (100.6 MHz, CDCl3):
d¼28.22 (C(CH3)3), 38.27
(b-CH2), 50.10 (a-C), 55.81 (OCH3), 67.57 (CH2), 80.23 (C(CH3)3),
104.37 (C7), 115.60 (C5), 120.81 (C4), 128.16 (C40), 128.28 (C30 and
C50), 128.47 (C20 and C60), 132.50 (C7a), 135.12 (C10), 140.58 (C3a),
155.58 (C]O urethane), 157.06 (C6), 157.15 (C2), 169.04 (C]O
amide), 170.96 (C]O ester) ppm. UV–Vis (ethanol, nm): lmax
(log
3
)¼325 (3.53). MS m/z (ESI, %): 523 (Mþþ23, 100).
C23H24N4O7S: calcd C 55.19, H 4.83, N 11.19, S 6.41; found C 55.49, H
5.00, N 10.88, S 6.46.
(log
3
)¼347 (3.22). MS m/z (ESI, %): 508 (Mþþ23, 100), 486
4.2.7. N-tert-Butyloxycarbonyl (6-thiocyanobenzothiazol-2-yl)aspara-
gine benzyl ester (3g). The product was isolated as a colourless
solid (0.424 g, 0.83 mmol, 66%). Mp¼169.0–172.0 ꢁC. IR (KBr, 1%):
([MþH]þ, 7). C24H27N3O6S: calcd C 59.37, H 5.60, N 8.65, S 6.60;
found C 59.42, H 5.76, N 8.55, S 6.73.
n
¼3326, 3230, 3094, 2973, 2940, 1742, 1730, 1701, 1594, 1524, 1447,
4.2.4. N-tert-Butyloxycarbonyl (6-ethoxybenzothiazol-2-yl) aspara-
gine benzyl ester (3d). The product was isolated as a colourless solid
1409, 1393, 1367, 1295, 1278, 1236, 1193, 1154, 1075, 1007, 990, 973,
925, 900, 869, 849, 757, 724 cmꢀ1. 1H NMR (300 MHz, CDCl3):
¼1.44
d