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N. Piens et al.
PAPER
1,3-Bis{3-[cis-3-(4-chlorophenoxy)-4-(4-chlorophenyl)-2-oxoaz-
etidin-1-yl]propyl}thymine (5d)
White powder; yield: 1.9 mmol (94%); Rf = 0.23 (hexane–EtOAc,
3:1), mp 95.0 °C; spectral data derived from the mixture of diaste-
reomers.
C), 82.00 (2 C), 82.04 (2 C), 110.2 (2 C), 116.86 (4 C), 116.92 (4
C), 127.25 (2 C), 127.29 (2 C), 127.32 (2 C), 127.5 (2 C), 129.2 (4
C), 129.3 (6 C), 129.5 (2 C), 129.69 (2 C), 129.73 (4 C), 129.8 (2
C), 134.6 (2 C), 134.7 (2 C), 134.9 (2 C), 135.3 (2 C), 138.7 (2 C),
151.3 (2 C), 155.2 (2 C), 155.3 (2 C), 163.5 (2 C), 165.7 (2 C), 166.0
(2 C).
IR (ATR): 2926, 1755 (CO), 1697 (CO), 1664 (CO), 1638 (CO),
1488, 1465, 1355, 1236, 1090, 1011, 822, 770 cm–1.
MS (70 eV): m/z (%) = 889/891/893/895/897/899/901 (M+ + H, 45).
1H NMR (400 MHz, CDCl3): δ = 1.73–1.82 (m, 4 H), 1.89–1.93 (m,
4 H), 1.93 (s, 6 H), 2.91–2.98 (m, 2 H), 3.04–3.11 (m, 2 H), 3.41–
3.48 (m, 2 H), 3.56–3.71 (m, 4 H), 3.80–3.88 (m, 2 H), 3.91–4.02
(m, 4 H), 4.99 (d, J = 4.4 Hz, 2 H), 5.11 (d, J = 4.4 Hz, 2 H), 5.41
(d, J = 4.4 Hz, 2 H), 5.42 (d, J = 4.4 Hz, 2 H), 6.67–6.70 (m, 8 H),
7.07–7.12 (m, 8 H), 7.10 (br s, 2 H), 7.27–7.32 (m, 16 H).
13C NMR (100 MHz, CDCl3): δ = 13.0 (2 C), 25.10, 25.13, 26.86,
26.90, 37.80, 37.83, 38.1 (2 C), 38.9 (2 C), 47.2 (2 C), 61.0 (2 C),
61.7 (2 C), 81.8 (2 C), 81.9 (2 C), 110.10, 110.11, 116.8 (8C), 127.1
(2 C), 127.4 (2 C), 128.7 (4 C), 128.8 (4 C), 129.2 (4 C), 129.3 (4
C), 129.90 (4 C), 129.92 (4 C), 131.2 (2 C), 131.5 (2 C), 134.7 (2
C), 135.1 (2 C), 138.8 (2 C), 151.3 (2 C), 155.2 (2 C), 155.3 (2 C),
163.6 (2 C), 165.6 (2 C), 166.0 (2 C).
HRMS (ESI): m/z [M + H]+ calcd for C41H35Cl6N4O6: 889.0688;
found: 889.0656.
1,3-Bis{3-[cis-2-oxo-3-phenoxy-4-(2,3,4-trimethoxyphe-
nyl)azetidin-1-yl]propyl}thymine (5g)
White powder; yield: 1.9 mmol (96%); mp 154.0 °C (EtOAc–hex-
ane, 30:1); spectral data derived from the mixture of diastereomers.
IR (ATR): 2940, 1753 (CO), 1697 (CO), 1664 (CO), 1639 (CO),
1598, 1494, 1466, 1419, 1293, 1231, 1094, 1010, 755, 734, 691 cm–1.
1H NMR (400 MHz, CDCl3): δ = 1.81–1.98 (m, 8 H), 1.93 (d, J =
1.0 Hz, 6 H), 2.94–3.01 (m, 2 H), 3.10 (dt, J = 14.3, 6.0 Hz, 2 H),
3.46 (dt, J = 14.5, 7.0 Hz, 2 H), 3.61 (dt, J = 14.5, 7.4 Hz, 2 H), 3.70–
3.75 (m, 2 H), 3.70 (s, 6 H), 3.72 (s, 6 H), 3.81–3.89 (m, 2 H), 3.81
(s, 6 H), 3.82 (s, 6 H), 3.83 (s, 6 H), 3.85 (s, 6 H), 3.97–4.03 (m, 4
H), 5.36 (d, J = 4.5 Hz, 2 H), 5.42 (d, J = 4.5 Hz, 2 H), 5.43 (d, J =
4.5 Hz, 2 H), 5.45 (d, J = 4.5 Hz, 2 H), 6.63 (d, J = 8.7 Hz, 2 H),
6.64 (d, J = 8.7 Hz, 2 H), 6.76–6.79 (m, 8 H), 6.83–6.90 (m, 4 H),
7.00 (d, J = 8.7 Hz, 2 H), 7.01 (d, J = 8.7 Hz, 2 H), 7.09–7.16 (m, 8
H), 7.19 (q, J = 1.0 Hz, 2 H).
MS (70 eV): m/z (%) = 821/3/5/7/9 (M+ + H, 40).
HRMS (ESI): m/z [M + H]+ calcd for C41H37Cl4N4O6: 821.1467;
found: 821.1447.
1,3-Bis{3-[cis-4-(2,4-dichlorophenyl)-2-oxo-3-phenoxyazetidin-
1-yl]propyl}thymine (5e)
13C NMR (100 MHz, CDCl3): δ = 13.0 (2 C), 25.4 (2 C), 26.9 (2 C),
37.8 (2 C), 38.1 (2 C), 39.0 (2 C), 47.4 (2 C), 55.6 (2 C), 55.91 (2
C), 55.93 (2 C), 56.3 (2 C), 60.6 (2 C), 60.7 (2 C), 61.16 (2 C), 61.24
(2 C), 81.8 (4 C), 106.9 (4 C), 109.9 (2 C), 115.58 (4 C), 115.64 (4
C), 118.0 (2 C), 118.4 (2 C), 121.8 (2 C), 122.0 (2 C), 123.1 (2 C),
123.2 (2 C), 129.1 (4 C), 129.2 (4 C), 139.1 (2 C), 141.66 (2 C),
141.72 (2 C), 151.3 (2 C), 152.6 (2 C), 152.7 (2 C), 153.7 (2 C),
154.0 (2 C), 156.9 (2 C), 157.0 (2 C), 163.7 (2 C), 166.3 (2 C), 166.9
(2 C).
White powder; yield: 1.7 mmol (87%); Rf = 0.13 (hexane–EtOAc,
1:1), mp 96.0 °C; spectral data derived from the mixture of diaste-
reomers.
IR (ATR): 2926, 1762 (CO), 1697 (CO), 1664 (CO), 1638 (CO),
1589, 1491, 1467, 1340, 1228, 1050, 811, 753, 691 cm–1.
1H NMR (400 MHz, CDCl3): δ = 1.81–1.99 (m, 8 H), 1.94 (s, 6 H),
2.97–3.10 (m, 4 H), 3.53 (dt, J = 14.2, 6.9 Hz, 2 H), 3.62 (dt, J =
14.2, 7.3 Hz, 2 H), 3.72 (dt, J = 13.6, 6.9 Hz, 2 H), 3.88 (dt, J = 13.6,
7.2 Hz, 2 H), 3.98–4.03 (m, 4 H), 5.51 (br s, 6 H), 5.56 (d, J = 4.2
Hz, 2 H), 6.78 (d, J = 7.9 Hz, 8 H), 6.89–6.95 (m, 4 H), 7.15 (br s,
2 H), 7.15–7.19 (m, 8 H), 7.27–7.38 (m, 12 H).
MS (70 eV): m/z (%) = 865 (M+ + H, 60).
HRMS (ESI): m/z [M + H]+ calcd for C47H53N4O12: 865.3660;
13C NMR (100 MHz, CDCl3): δ = 13.0 (2 C), 25.4 (2 C), 26.9 (2 C),
38.30, 38.34, 38.5 (2 C), 38.9 (2 C), 47.3 (2 C), 57.8 (2 C), 58.3 (2
C), 81.97 (2 C), 82.00 (2 C), 110.2 (2 C), 115.5 (4 C), 115.6 (4 C),
122.3 (2 C), 122.5 (2 C), 127.2 (2 C), 127.3 (2 C), 129.30 (4 C),
129.33 (2 C), 129.41 (4 C), 129.42 (2 C), 129.5 (2 C), 129.6 (2 C),
129.8 (2 C), 129.9 (2 C), 130.0 (2 C), 134.7 (2 C), 134.8 (2 C), 135.1
(2 C), 138.7 (2 C), 151.3 (2 C), 156.6 (2 C), 156.8 (2 C), 163.6 (2
C), 166.1 (2 C), 166.4 (2 C).
found: 865.3680.
1,3-Bis(3-{[2-(4-chlorophenoxy)-1-(4-chlorophenyl)-2-methoxy-
carbonylethyl]amino}propyl)thymine (6a); Typical Procedure
To a solution of 5d (0.82 g, 1 mmol, 1 equiv) in MeOH (20 mL) was
added 3 M HCl in MeOH (3.3 mL), and the mixture was refluxed
for 48 h. MeOH was removed in vacuo, followed by the addition of
anhyd CH2Cl2 (20 mL) and Et3N (0.40 g, 4 mmol, 4 equiv). Subse-
quently, the resulting mixture was heated under reflux for 4 h, after
which the solvent was evaporated under reduced pressure. Addition
of anhyd Et2O, filtration of the precipitated Et3N·HCl, drying of the
filtrate (MgSO4), filtration of the drying agent and removal of the
solvent in vacuo yielded 6a, which was further purified by column
chromatography (silica gel, hexane–EtOAc, 2:3) to give a white
powder; yield: 0.5 mmol (51%); Rf = 0.33 (hexane–EtOAc, 2:3), mp
66.0 °C; spectral data derived from the mixture of diastereomers.
MS (70 eV): m/z (%) = 821/3/5/7/9 (M+ + H, 100).
HRMS (ESI): m/z [M + H]+ calcd for C41H37Cl4N4O6: 821.1467;
found: 821.1455.
1,3-Bis{3-[cis-3-(4-chlorophenoxy)-4-(2,4-dichlorophenyl)-2-
oxoazetidin-1-yl]propyl}thymine (5f)
White powder; yield: 1.8 mmol (92%); Rf = 0.10 (hexane–EtOAc,
1:1), mp 92.0 °C; spectral data derived from the mixture of diaste-
reomers.
IR (ATR): 3328 (NH), 2953, 1751 (CO), 1696 (CO), 1664 (CO),
1637 (CO), 1489, 1466, 1232, 1207, 1089, 824, 734, 701 cm–1.
IR (ATR): 2928, 1759 (CO), 1697 (CO), 1664 (CO), 1639 (CO),
1488, 1467, 1353, 1235, 1048, 822, 734, 702 cm–1.
1H NMR (400 MHz, CDCl3): δ = 1.71–1.80 (m, 8 H), 1.90 (d, J =
0.9 Hz, 6 H), 2.31 (br s, 4 H), 2.43–2.48 (m, 8 H), 3.57 (s, 6 H), 3.62
(s, 6 H), 3.66–3.83 (m, 4 H), 3.90–4.02 (m, 4 H), 4.19 (d, J = 5.5 Hz,
2 H), 4.20 (d, J = 5.9 Hz, 2 H), 5.57 (d, J = 5.9 Hz, 2 H), 5.60 (d, J =
5.5 Hz, 2 H), 6.75 (d, J = 9.0 Hz, 4 H), 6.78 (d, J = 9.0 Hz, 4 H),
6.92 (q, J = 0.9 Hz, 2 H), 7.18 (d, J = 9.0 Hz, 4 H), 7.19 (d, J = 9.0
Hz, 4 H), 7.28–7.34 (m, 16 H).
13C NMR (100 MHz, CDCl3): δ = 13.0 (2 C), 27.8 (2 C), 28.8 (2 C),
39.2 (2 C), 43.3 (2 C), 44.2 (2 C), 47.1 (2 C), 52.3 (2 C), 52.4 (2 C),
63.8 (2 C), 63.9 (2 C), 81.7 (2 C), 81.9 (2 C), 109.6 (2 C), 116.7 (4
C), 116.8 (4 C), 127.0 (2 C), 127.3 (2 C), 128.7 (4 C), 128.9 (4 C),
1H NMR (400 MHz, CDCl3): δ = 1.80–1.87 (m, 4 H), 1.89–2.02 (m,
4 H), 1.93 (s, 6 H), 2.96–3.03 (m, 2 H), 3.07 (dt, J = 14.3, 6.2 Hz, 2
H), 3.54 (dt, J = 14.7, 6.9 Hz, 2 H), 3.62 (dt, J = 14.7, 7.3 Hz, 2 H),
3.72 (dt, J = 13.9, 7.1 Hz, 2 H), 3.88 (dt, J = 13.9, 6.9 Hz, 2 H), 3.93–
4.07 (m, 4 H), 5.46 (d, J = 4.6 Hz, 4 H), 5.50 (d, J = 4.6 Hz, 2 H),
5.55 (d, J = 4.6 Hz, 2 H), 6.71–6.75 (m, 8 H), 7.09–7.13 (m, 8 H),
7.13 (br s, 2 H), 7.26–7.37 (m, 12 H).
13C NMR (100 MHz, CDCl3): δ = 13.0 (2 C), 25.4 (2 C), 26.9 (2 C),
38.37, 38.41, 38.5 (2 C), 38.8 (2 C), 47.2 (2 C), 57.7 (2 C), 58.1 (2
Synthesis 2014, 46, 2436–2444
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