1638
A. Robin et al.
PAPER
2-N-tert-Butoxycarbonylamino-5-ethoxycarbonylthiophene
6-Amino-2,3-di(ethoxycarbonyl)-2H-thiopyran (2c)
Yield: 56%; yellow oil.
(7c)
Yield: 79%; white solid; mp 159 °C.
IR (film): 3335 (m), 1732 (w), 1511 (w), 1265 (w), 1183 (w) cm–1.
IR (film): 3267 (m), 1719 (m), 167 (m), 1565 (m), 1507 (m), 1271
(w), 1247 (w), 1156 (w) cm–1.
1H NMR (200 MHz, CDCl3): d = 1.34 (t, J = 7.2 Hz, 3 H, CH3CH2),
1.53 [s, 9 H, (CH3)3], 4.30 (q, J = 7.2 Hz, 2 H, CH2), 6.47 (d, J = 4.1
Hz, 1 H, C3-H), 7.57 (d, J = 4.1 Hz, 1 H, C4-H), 7.65 (br s, 1 H,
NH).
13C NMR (50 MHz, CDCl3): d = 14.4 (CH3CH2), 28.3 (3 × CH3),
60.9 (CH2), 82.4 [C(CH3)3, 110.4 (C3-H), 123.3 (C5), 132.3
(C4-H), 147.4 (C2), 152.1 (NCO), 163.2 (CO2).
1H NMR (200 MHz, CDCl3): d = 1.24, 1.29 (2 × t, J = 6.6 Hz, 2 × 3
H, 2 × CH3), 4.15, 4.18 (2 × q, 2 × 2 H, J = 6.6 Hz, 2 × CH2), 4.46
(br s, 2 H, NH2), 4.78 (s, 1 H, CH), 5.46 (d, J = 7.3 Hz, 1 H, C5-H),
7.38 (d, J = 7.3 Hz, 1 H, C4-H).
13C NMR (50 MHz, CDCl3): d = 14.1, 14.5 (2 × CH3), 41.1 (C2-H),
60.5, 62.0 (2 × CH2), 95.2 (C5-H), 106.2 (C3), 138.9 (C4-H), 148.1
(C6), 166.3, 170.4 (2 × CO2).
MS (EI): m/z (%) = 257 (12) [M+], 184 (100), 156 (64), 110 (20), 29
(16).
HRMS (EI+): m/z [M]+ calcd for C11H15NO4S: 257.0722; found:
257.0723.
MS (EI): m/z (%) = 272 (26) [M+], 215 (32), 171 (27), 59 (49), 57
(100), 41 (36).
2-N-tert-Butoxycarbonylamino-5-p-chlorobenzoylthiophene
(7d)
2-N-Acylaminothiophenes 7; General Procedure
A solution of acceptor-substituted halomethyl (ethyl bromoacetate
for 7a, 7c; 2-bromo-4¢-chloroacetophenone for 7b, 7d; benzyl bro-
moacetate for 7e; chloroacetone for 7f; bromoacetonitrile for 7g;
1,3-dichloroacetone for 7h) (2.2 mmol for 7b, 7d; 4 mmol for 7a,
7c, 7e, 7f, 7h; 6 mmol for 7g) and thiadiene 5a or 5b (2 mmol) in
THF (15 mL, for 7a, 7c, 7e) or CH2Cl2 (15 mL, for 7b, 7d, 7f, 7g,
7h) was stirred for 1 h at r.t. Then, Et3N (8 mmol for 7a, 7c, 7e, 7f;
4.4 mmol for 7b, 7d, 7g, 7h) was added and the reaction mixture
was further stirred at reflux for 18 h. The solution was washed with
water [20 mL, after dilution with CH2Cl2 (30 mL) for 7a, 7c, 7e].
The aqueous phase was extracted with CH2Cl2 (2 × 20 mL). The
combined organic layers were washed with water (2 × 30 mL), dried
(MgSO4) and then evaporated in reduced pressure. The residue was
purified by washing with Et2O for 7b, 7d; by chromatography on
silica using CH2Cl2 as eluent for 7a, 7c, 7g, 7h; petroleum ether–
EtOAc (7:3) for 7e; petroleum ether–CH2Cl2 (5:5) for 7f.
Yield: 71%; white solid; mp 185 °C.
IR (film): 3245 (s), 1719 (m), 1448 (w), 1287 (m), 1247 (w), 1155
(w) cm–1.
1H NMR (200 MHz, CDCl3): d = 1.53 [s, 9 H, (CH3)3], 6.59 (d, J =
4.3 Hz, 1 H, C3-H), 7.42 (d, J = 4.3 Hz, 1 H, C4-H), 7.44 (d, J = 8.4
Hz, 2 H, 2 × CHarom), 7.76 (d, J = 8.4 Hz, 2 H, 2 × CHarom), 7.82 (br
s, 1 H, NH).
13C NMR (50 MHz, CDCl3): d = 28.3 (3 × CH3), 82.9 [C(CH3)3],
111.3 (C3-H), 128.8, 130.4 (2 × 2 Carom), 133.0 (C4-H), 134.9 (C5),
137.0, 138.1 (2 × Carom), 150.8 (C2), 151.8 (NCO), 187.0 (CO).
MS (EI): m/z (%) = 337 (2) [M+], 281 (27), 237 (20), 57 (100), 41
(29).
2-N-tert-Butoxycarbonylamino-5-benzoxycarbonylthiophene
(7e)
2-N-Acetylamino-5-ethoxycarbonylthiophene (7a)
Yield: 79%; orange solid; mp 161 °C.
Yield: 74%; white solid; mp 122 °C.
IR (film): 3293 (s), 1718 (m), 1560 (m), 1506 (m), 1457 (m), 1250
(w), 1155 (w) cm–1.
1H NMR (200 MHz, CDCl3): d = 1.50 [s, 9 H, (CH3)3], 5.29 (s, 2 H,
CH2), 6.47 (d, J = 4.3 Hz, 1 H, C3-H), 7.36 (m, 5 H, 5 × CHarom),
7.61 (d, J = 4.3 Hz, 1 H, C4-H), 7.96 (br s, 1 H, NH).
IR (film): 3205 (s), 1713 (w), 1657 (m), 1568 (w), 1449 (w), 1255
(w), 1093 (w) cm–1.
1H NMR (200 MHz, CDCl3): d = 1.35 (t, J = 7.0 Hz, 3 H, CH3CH2),
2.25 (s, 3 H, CH3CO), 4.32 (q, J = 7.0 Hz, 2 H, CH2), 6.59 (d, J =
4.2 Hz, 1 H, C3-H), 7.59 (d, J = 4.2 Hz, 1 H, C4-H), 8.67 (br s, 1 H,
NH).
13C NMR (50 MHz, CDCl3): d = 14.5 (CH3CH2), 23.3 (CH3CO),
61.0 (CH2), 111.7 (C3-H), 124.4 (C5), 131.6 (C4-H), 145.5 (C2),
163.3 (CO2), 167.3 (CO).
13C NMR (50 MHz, CDCl3): d = 28.3 (3 × CH3), 66.5 (CH2), 82.4
[C(CH3)3], 110.5 (C3-H), 122.7 (C5), 128.1, 128.2, 128.6 (5 ×
Carom), 132.9 (C4-H), 136.0 (Carom), 147.9 (C2), 152.0 (NCO), 163.0
(CO2).
MS (EI): m/z (%) = 333 (3) [M+], 277 (26), 170 (17), 126 (16), 91
(68), 57 (100), 41 (23).
HRMS (EI+): m/z [M]+ calcd for C17H19NO4S: 333.1035; found:
MS (EI): m/z (%) = 213 (45) [M+], 171 (100), 143 (52), 126 (67), 99
(45), 43 (73).
333.1030.
2-N-Acetylamino-5-p-chlorobenzoylthiophene (7b)
Yield: 82%; orange solid; mp 109 °C.
5-Acetyl-2-N-tert-butoxycarbonylaminothiophene (7f)
Yield: 72%; white solid; mp 171 °C.
IR (film): 3277 (m), 1683 (m), 1595 (w), 1565 (w), 1443 (w) and
1287 (w) cm–1.
1H NMR (200 MHz, CD3COCD3): d = 2.19 (s, 3 H, CH3), 6.77 (d,
J = 4.2 Hz, 1 H, C3-H), 7.50 (d, J = 4.2 Hz, 1 H, C4-H), 7.57 (d,
J = 8.7 Hz, 2 H, 2 × CHarom), 7.82 (d, J = 8.7 Hz, 2 H, 2 × CHarom),
10.9 (br s, 1 H, NH).
13C NMR (50 MHz, DMSO): d = 22.7 (CH3), 112.2 (C3-H), 128.7,
130.4, 131.8 (5 × Carom), 135.0 (C4-H), 136.6 (C5), 136.8 (Carom),
149.4 (C2), 167.7 (NCO), 186.2 (CO).
IR (film): 3234 (s), 1720 (m), 1622 (m), 1563 (m), 1501 (m), 1449
(m), 1281 (w), 1247 (w), 1155 (w) cm–1.
1H NMR (200 MHz, CDCl3): d = 1.52 [s, 9 H, (CH3)3], 2.49 (s, 3 H,
CH3CO), 6.59 (d, J = 4.2 Hz, 1 H, C3-H), 7.50 (d, J = 4.2 Hz, 1 H,
C4-H), 8.20 (br s, 1 H, NH).
13C NMR (50 MHz, CDCl3): d = 26.3 (CH3CO), 28.3 (3 × CH3),
82.5 [C(CH3)3], 111.2 (C3-H), 132.3 (C4-H), 133.9 (C5), 150.0
(C2), 152.0 (NCO), 190.9 (CO).
MS (EI): m/z (%) = 281 (16), 279 (40) [M+], 239 (38), 237 (100),
126 (73), 110 (20), 43 (43).
MS (EI): m/z (%) = 241 (4) [M+], 185 (23), 141 (18), 126 (17), 57
(100), 41 (30).
Synthesis 2004, No. 10, 1633–1640 © Thieme Stuttgart · New York