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Vol. 51, No. 3
1H), 4.66 (m, 2H), 7.28 (m, 5H). 13C-NMR (100 MHz, CDCl3) d: 28.6, 31.4,
48.7, 52.2, 57.5, 58.8, 73.8, 78.2, 101.3, 127.0, 128.2, 129.0, 136.3. HR-MS
m/z: Calcd for C16H23NO3, 277.1672. Found: 277.1702. Anal. Calcd for
C16H23NO3: C, 69.29; H, 8.36; N, 5.05. Found: C, 69.05; H, 8.25; N, 4.95.
4-[2-(5-Benzyl-2,2-dimethyltetrahydro[1,3]dioxolo[4,5-c]pyrrol-4-yl)-
ethoxy]benzaldehyde (21) The title compound 21 (1.77 g, 76% yield) was
prepared as an oil from 2-(5-benzyl-2,2-dimethyltetrahydro[1,3]dioxol[4,5-
c]pyrrol-4-yl)ethanol (20) (1.69 g, 6.09 mmol), 4-hydroxybenzaldehyde
(967 mg, 7.92 mmol), Ph3P (2.4 g, 9.14 mmol) and DEAD (1.44 ml, 9.14
mmol) by a procedure analogous to that described for the preparation of
compound 16. IR (CHCl3) nmax cmϪ1: 2972, 1687, 1600, 1256, 1159. 1H-
NMR (400 MHz, CDCl3) d: 1.34 (s, 3H), 1.58 (s, 3H), 2.05 (m, 1H), 2.26
(m, 2H), 2.43 (m, 1H), 7.04 (m, 2H), 7.27 (m, 5H), 7.86 (m, 2H), 9.91 (s,
1H). 13C-NMR (100 MHz, CDCl3) d: 28.8, 48.7, 52.0, 57.6, 68.5, 73.8, 78.5,
101.5, 114.5, 127.0, 128.2, 128.3, 129.0, 130.5, 136.5, 164.5, 190.1. HR-MS
m/z: Calcd for C23H27NO4, 381.1933. Found: 381.1945. Anal. Calcd for
C23H27NO4: C, 72.42; H, 7.13; N, 3.67. Found: C, 72.09; H, 7.30; N, 3.59.
5-{4-[2-(5-Benzyl-2,2-dimethyltetrahydro[1,3]dioxolo[4,5-c]pyrrol-4-
yl)ethoxy]benzylidene}thiazolidine-2-one (22) The title compound 22
(600 mg, 95% yield) was prepared as yellow solid from 4-[2-(5-benzyl-2,2-
dimethyltetrahydro[1,3]dioxol[4,5-c]pyrrol-4-yl)ethoxy]benzaldehyde (21)
(500 mg, 1.31 mmol), TZD (230 mg, 1.97 mmol), and with catalytic amount
of piperidium acetate by a similar to that described for the preparation of
yield) was prepared as an oil from 4-[2-(1-benzyl-3,4-bis-benzyloxypyrro-
lidin-2-yl)ethoxy]benzaldehyde (23b) (200 mg, 0.384 mmol) TZD (90.0 mg,
0.768 mmol) and with catalytic amount of piperidinium acetate by a similar
to that described for the preparation of compound 5. IR (CHCl3) nmax cmϪ1
:
1
2930, 1698, 1604, 1377, 1266. H-NMR (400 MHz, CDCl3) d: 2.07—2.27
(m, 2H), 2.56 (m, 1H), 3.18 (m, 2H), 3.55 (m, 1H), 3.97—4.19 (m, 4H),
4.54—4.83 (m, 4H), 6.85 (m, 2H), 7.32 (m, 17H), 7.92 (s, 1H). 13C-NMR
(100 MHz, CDCl3) d: 28.5, 48.5, 52.5, 57.5, 68.1, 73.5, 74.0, 78.4, 114.1,
120.5, 126.5, 126.8, 127.0, 127.6, 128.2, 128.4, 129.0, 136.3, 137.2, 142.5,
158.0, 167.5, 166.0. HR-MS m/z: Calcd for C37H36N2O5S, 620.2336. Found:
620.2350. Anal. Calcd for C37H36N2O5S: C, 71.59; H, 5.85; H, 4.51. Found:
C, 71.70; H, 5.90; N, 4.45.
Benzoic Acid-2-(5-benzyl-2,2-dimethyltetrahydro[1,3]dioxolo[4,5-c]-
pyrrol-4-yl)ethyl Ester (25) The title compound 25 (13.6 g, 93% yield)
was prepared as an oil from 2-(5-benzyl-2,2-dimethyltetrahydro[1,3]diox-
olo[4,5-c]pyrrol-4-yl)ethanol (20) (10.6 g, 38.36 mmol) benzoic anhydride
(13 g, 57.5 mmol) and with catalytic amount of DMAP by a similar to that
described for the preparation of compound 7. IR (CHCl3) nmax cmϪ1: 2934,
1
2791, 1717, 1452, 1378, 1275, 1112, 712. H-NMR (400 MHz, CDCl3) d:
1.32 (s, 3H), 1.57 (s, 3H), 2.06 (dd, Jϭ11.2, 4.6 Hz, 1H), 2.29—2.35 (m,
3H), 3.07 (d, Jϭ11.2 Hz, 1H), 3.24 (d, Jϭ13.6 Hz, 1H), 4.10 (d, Jϭ13.6 Hz,
1H), 4.51—4.69 (m, 4H), 7.24—7.59 (m, 8H), 8.10 (d, Jϭ6.2 Hz, 2H). 13C-
NMR (100 MHz, CDCl3) d: 28.0, 28.5, 48.7, 52.5, 57.5, 62.1, 73.8, 78.0,
100.5, 127.0, 128.2, 128.4, 129.4, 129.0, 129.5, 132.8, 136.3, 167.5. HR-MS
m/z: Calcd for C23H27NO4, 381.1933. Found: 981.1940. Anal. Calcd for
C23H27NO4: C, 72.42; H, 7.13; N, 3.67. Found: C, 72.50; H, 7.50; N, 3.90.
Benzoic Acid-2-(1-benzyl-3,4-diethoxypyrrolidin-2-yl)ethyl Ester (26)
The title compound 26 (2.18 g, 52% yield) was prepared as an oil from ben-
zoic acid 2-(5-benzyl-2,2-dimethyltetrahydro[1,3]dioxolo[4,5-c]pyrrol-4-
yl)ethyl ester (4.0 g, 10.48 mmol) TFA–H2O, ethyl iodide, NaH, and catalytic
amount of TBAI by a similar to that described for the preparation of com-
1
compound 5. IR (KBr) nmax cmϪ1: 2936, 1697, 1597, 1510, 1254. H-NMR
(400 MHz, CDCl3) d: 1.35 (s, 3H), 1.58 (s, 3H), 2.10 (m, 1H), 2.27 (m, 2H),
2.45 (m, 1H), 3.10 (m, 1H), 3.25 (m, 1H), 4.10 (m, 1H), 4.27 (m, 2H), 4.64
(m, 2H), 7.47—7.02 (m, 9H), 7.80 (s, 1H). 13C-NMR (100 MHz, CDCl3) d:
28.5, 28.8, 48.5, 52.5, 57.5, 68.5, 73.8, 78.2, 101.5, 114.5, 120.6, 126.8,
127.0, 128.2, 136.3, 142.5, 158.0, 167.0, 167.5. HR-MS m/z: Calcd for
C26H28N2O5S, 480.1712. Found: 480.1795. Anal. Calcd for C26H28N2O5S: C,
64.98; H, 5.87; N, 5.83. Found: C, 65.01; H, 5.95; N, 5.75.
1
pound 23. IR (CHCl3) nmax cmϪ1: 2974, 1717, 1376, 1275, 1113. H-NMR
4-[2-(1-Benzyl-3,4-diethoxypyrrolidin-2-yl)ethoxy]benzaldehyde (23a)
The title compound 23a (300 mg, 58% yield) was prepared as an oil from 5-
{4-[2-(5-benzyl-2,2-dimethyltetrahydro[1,3]dioxol[4,5-c]pyrrol-4-
yl)ethoxy]benzaldehyde (21) (500 mg, 1.31 mmol), TFA–H2O (10 ml, 4/1
v/v), sodium hydride (60% in mineral oil, 79 mg, 1.97 mmol), and ethyl io-
dide (0.42 mg, 5.24 mmol) by a similar to that described for the preparation
of compounds 4 and 7. IR (CHCl3) nmax cmϪ1: 2934, 2796, 1688, 1600,
(400 MHz, CDCl3) d: 1.23 (q, Jϭ5.5 Hz, 6H), 2.00 (m, 1H), 2.20 (m, 1H),
2.53 (m, 1H), 2.80 (m, 1H), 3.15 (m, 2H), 3.48—3.95 (m, 7H), 4.43 (t,
Jϭ6.5 Hz, 2H), 7.28—7.60 (m, 8H), 8.07 (d, Jϭ6.0 Hz, 2H). 13C-NMR
(100 MHz, CDCl3) d: 15.0, 28.9, 49.0, 53.0, 57.5, 60.0, 61.1, 62.5, 75.5,
79.2, 127.0, 128.2, 128.4, 129.0, 129.7, 136.0, 137.5, 167.5. HR-MS m/z:
Calcd for C24H31NO4, 397.2245. Found: 397.2290. Anal. Calcd for
C24H31NO4: C, 72.52; H, 7.86; N, 3.52. Found: C, 72.59; H, 7.99; N, 3.60.
Benzoic Acid-2-(3,4-diethoxypyrrolidin-2-yl)ethyl Ester (27a) The
title compound 27a (15 g, 76% yield) was prepared as an oil from benzoic
acid-2-(1-benzyl-3,4-diethoxypyrrolidin-2-yl)ethyl ester (26) (2.55 g, 6.42
mmol) 20% Pd(OH)2 (1.1 g) under H2 atmosphere by a similar to that de-
scribed for the preparation of compound 19. IR (CHCl3) nmax cmϪ1: 3419,
2983, 1732, 1379, 1210. 1H-NMR (400 MHz, CDCl3) d: 1.23 (m, 6H),
1.99—2.16 (m, 2H), 2.55 (br s, 1H), 3.04 (m, 2H), 3.20 (m, 1H), 3.55 (m,
3H), 3.78 (m, 2H), 3.95 (m, 1H), 4.45 (t, Jϭ6.5 Hz, 2H), 7.41—7.58 (m,
3H), 8.05 (d, Jϭ6.2 Hz, 2H). 13C-NMR (100 MHz, CDCl3) d: 15.5, 30.0,
45.0, 50.5, 60.5, 61.1, 61.8, 76.3, 80.5, 128.5, 129.7, 130.5, 132.8, 167.0.
HR-MS m/z: Calcd for C17H25NO4, 307.1777. Found: 307.1790. Anal. Calcd
for C17H25NO4: C, 66.43; H, 8.20; N, 4.56. Found: C, 66.50; H, 8.55; N,
4.85.
1
1255, 1212. H-NMR (400 MHz, CDCl3) d: 1.23 (m, 6H), 2.00—2.30 (m,
2H), 2.91 (m, 1H), 3.07 (m, 2H), 3.52 (m, 4H), 3.75 (m, 1H), 3.91 (m, 3H),
4.26 (m, 2H), 7.01 (d, Jϭ8.7 Hz, 2H), 7.25 (m, 5H), 7.83 (d, Jϭ8.7 Hz, 2H),
9.89 (s, 1H). 13C-NMR (100 MHz, CDCl3) d: 15.5, 28.8, 48.7, 52.5, 57.5,
60.8, 61.6, 68.5, 74.1, 78.5, 114.7, 127.0, 128.2, 128.3, 129.0, 130.3, 136.5,
164.6, 190.0. HR-MS m/z: Calcd for C24H31NO4, 397.2245. Found:
397.2210. Anal. Calcd for C24H31NO4: C, 72.52; H, 7.86; N, 3.52. Found: C,
72.61; H, 7.70; N, 3.65.
4-[2-(1-Benzyl-3,4-bis-benzyloxypyrrolidin-2-yl)ethoxy]benzaldehyde
(23b) The deprotection and O-benzylation of the title compound 4-[2-(5-
benzyl-2,2-dimethyltetrahydro[1,3]dioxol[4,5-c]pyrrol-4-yl)ethoxy]benz-
aldehyde 21 (200 mg, 70 mmol) was conducted in a similar procedure as
employed in the synthesis of the title compounds 4 and 7. IR (CHCl3) nmax
cmϪ1: 2920, 1685, 1600, 1256, 1158. 1H-NMR (400 MHz, CDCl3) d: 2.05—
2.35 (m, 2H), 2.53 (m, 1H), 3.15 (m, 2H), 3.50 (d, Jϭ13.5 Hz, 1H), 4.00 (d,
Jϭ13.5 Hz, 1H), 4.05—4.20 (m, 15H), 7.74 (d, Jϭ8.7 Hz, 2H), 9.89 (s, 1H).
13C-NMR (100 MHz, CDCl3) d: 28.5, 48.7, 52.5, 57.5, 68.1, 73.5, 73.8,
74.0, 78.4. HR-MS m/z: Calcd for C34H35NO4, 521.2557. Found: 521.2580.
Anal. Calcd for C34H35NO4: C, 78.28; H, 6.76; N, 2.69. Found: C, 78.50; H,
6.90; N, 2.55.
5-{4-[2-(1-Benzyl-3,4-diethoxypyrrolidin-2-yl)ethoxy]benzylidene}thi-
azolidine-2,4-dione (24a) The title compound 24a (30 mg, 36% yield)
was prepared as an oil from 4-[2-(1-benzyl-3,4-dimethypyrrolidin-2-yl)-
ethoxy]benzaldehyde (23a) (69 mg, 0.17 mmol), TZD (40 mg, 0.35 mmol)
and with catalytic amount of piperidinium acetate by a similar to that de-
scribed for the preparation of compound 5. IR (CHCl3) nmax cmϪ1: 2975,
1697, 1595, 1510, 1252, 1177. 1H-NMR (400 MHz, CDCl3) d: 1.23 (m, 6H),
2.20 (m, 2H), 2.70 (m, 1H), 3.05 (m, 1H), 3.30 (m, 1H), 3.52 (m, 3H),
3.63—4.02 (m, 5H), 4.19 (m, 2H), 6.93—7.42 (m, 9H), 7.69 (s, 1H). 13C-
NMR (100 MHz, CDCl3) d: 15.0, 28.5, 48.6, 52.5, 57.9, 60.5, 61.5, 68.5,
74.1, 78.5, 114.5, 120.5, 126.5, 126.8, 127.5, 128.2, 129.0, 136.3, 142.5,
158.5, 166.5, 167.1. HR-MS m/z: Calcd for C27H32N2O5S, 496.2024. Found:
496.2094. Anal. Calcd for C27H32N2O5S: C, 65.30; H, 6.49; N, 5.64. Found:
C, 65.50; H, 6.57; N, 5.95.
2-(2-Benzyloxyethyl)3,4-diethoxy-N-methylpyrrolidine (28a) The title
compound 28a (318 mg, 61% yield) was prepared from benzoic acid-(3,4-
diethoxypyrrolidin-2-yl)ethyl ester (27) (500 mg, 1.62 mmol), para-
formaldehyde (488 mg, 16.3 mmol), sodium cyanoborohydride (153 mg,
2.43 mmol), and acetic acid by a similar to that described for the preparation
of compound 19. The following compound 28b, c were prepared by a similar
to the procedure above. IR (CHCl3) nmax cmϪ1: 2794, 1717, 1275, 1113, 715.
1H-NMR (400 MHz, CDCl3) d: 1.90—2.55 (m, 7H), 3.18 (m, 1H), 3.46—
3.94 (m, 6H), 4.44 (m, 2H), 7.46 (m, 2H), 7.58 (m, 1H), 8.07 (m, 2H). 13C-
NMR (100 MHz, CDCl3) d: 15.5, 27.5, 37.6, 51.5, 55.0, 61.1, 62.1, 62.5,
73.8, 77.9, 128.4, 129.7, 130.5, 132.5, 132.9, 167.7. HR-MS m/z: Calcd for
C18H27NO4, 321.1930. Found: 321.1955. Anal. Calcd for C18H27NO4: C,
67.26; H, 8.47; N, 4.36. Found: C, 67.35; H, 8.60; N, 4.55.
2-(2-Benzoyloxyethyl)3,4-diethoxy-N-propylpyrrolidine (28b) Yield:
280 mg, 58%. IR (CHCl3) nmax cmϪ1: 2973, 1734, 1623, 1509, 1252, 1176.
1H-NMR (400 MHz, CDCl3) d: 0.88—1.28 (m, 9H), 1.90 (m, 2H), 2.20 (m,
1H), 2.55 (m, 1H), 2.65 (m, 1H), 2.80 (m, 1H), 3.17 (m, 1H), 3.53 (m, 3H),
3.79—3.99 (m, 3H), 4.56 (m, 2H), 7.47 (m, 2H), 7.57 (m, 1H), 8.05 (m,
2H). 13C-NMR (100 MHz, CDCl3) d: 11.5, 15.5, 23.1, 28.1, 49.5, 52.9, 54.5,
60.9, 61.5, 62.3, 74.1, 78.5, 128.5, 129.9, 130.5, 167.0. HR-MS m/z: Calcd
for C20H31NO4, 349.2245. Found: 349.2279. Anal. Calcd for C20H31NO4: C,
68.74; H, 8.94; N, 4.01. Found: C, 68.90; H, 8.79; N, 4.20.
5-{4-[2-(1-Benzyl-3,4-bis-benzyloxypyrrolidin-2-yl)ethoxy]benzyli-
dene}thiazolidine-2,4-dione (24b) The title compound 24b (200 mg, 84%