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3.4.3.
(2%S,5S)-5-Benzyl-2%-methoxymethyl-[1,1%]-
3.4.7.
(2%S,5S)-5-(4-Fluorobenzyl)-2%-methoxymethyl-
bipyrrolidinyl-2-one 10a. Oil; [h]2D5=−64.4 (c 0.57,
[1,1%]bipyrrolidinyl-2-one 10e. Oil; [h]2D5=−59.7 (c 1.37,
1
1
CHCl3). H NMR (CDCl3) l (ppm): 1.60–1.93 (m, 5H,
CHCl3). H NMR (CDCl3) l (ppm): 1.58–1.91 (m, 5H,
4Hpyrrolidine+1Hsmp), 2.07–2.45 (m, 4H, 3Hsmp+1H
CH2Ar), 3.15–3.21 (m, 1H, Hsmp), 3.33–3.42 (m, 7H,
OCH3+2Hsmp+NCH+1H CH2Ar), 3.63–3.69 (m, 1H,
4Hpyrrolidine+1Hsmp), 2.05–2.42 (m, 4H, 3Hsmp+1H
CH2Ar), 3.12–3.18 (m, 1H, Hsmp), 3.23–3.41 (m, 7H,
OCH3+2Hsmp+NCH+1H CH2Ar), 3.61–3.68 (m, 1H,
Hsmp), 4.00–4.08 (m, 1H, Hsmp), 7.18–7.32 (m, 5H,
Hsmp), 3.99–4.06 (m, 1H, Hsmp), 6.96 (t, J=8.6, 2H,
Harom). 13C NMR (CDCl3) l (ppm): 22.6 (CH2), 23.3
(CH2), 27.1 (CH2), 29.4 (CH2), 40.5 (CH2Ar), 50.6
(NCH2), 58.8 (OCH3), 59.5 (NCH), 60.4 (NCH), 75.1
(CH2O), 126.4 (CHarom), 128.5 (2 CHarom), 129.1 (2
CHarom), 138.0 (Cq), 173.9 (C=O). IR (CHCl3) cm−1:
2950, 1689, 1511, 1223, 1100. Anal. calcd for
C17H24N2O2 (288) C, 70.80; H, 8.39; N, 9.71. Found C,
70.98; H, 8.16; N, 9.96.
Harom), 7.14 (t, J=8.6, 2H, Harom). 13C NMR (CDCl3)
l (ppm): 22.6 (CH2), 23.2 (CH2), 27.0 (CH2), 29.4
(CH2), 39.7 (CH2Ar), 50.6 (NCH2), 58.8 (OCH3), 59.4
(NCH), 60.4 (NCH), 75.1 (CH2O), 115.3 (d, J=20.8, 2
CHarom), 130.4 (d, J=7.9, 2 CHarom), 133.6 (d, J=3.0,
Cq), 161.6 (d, J=242.6, C-F), 174.0 (CꢁO). IR (CHCl3)
cm−1: 2942, 1687, 1509, 1210, 1104. Anal. calcd for
C17H23FN2O2 (306) C, 66.65; H, 7.57; N, 9.14. Found
C, 66.91; H, 7.74; N, 9.24.
3.4.4.
(2%S,5S)-2%-Methoxymethyl-5-(4-methylbenzyl)-
[1,1%]bipyrrolidinyl-2-one 10b. Oil; [h]2D5=−21.1 (c 0.30,
3.5. General procedure for the preparation of the 5-
arylmethylpyrrolidin-2-ones 8a–e
1
CHCl3). H NMR (CDCl3) l (ppm): 1.59–1.91 (m, 5H,
4Hpyrrolidine+1Hsmp), 2.05–2.42 (m, 7 H, CH3+3Hsmp+1H
CH2Ar), 3.17–3.23 (m, 1H, Hsmp), 3.28–3.44 (m, 7H,
OCH3+2Hsmp+NCH+1H CH2Ar), 3.63–3.72 (m, 1H,
To a solution of arylmethylhydrazide 10a–e (1 mmol) in
methanol (40 ml) was added MMPP (2.5 mmol, 1.24 g).
The reaction mixture was stirred at room temperature
until no starting material remained (TLC monitoring).
The mixture was then poured in CH2Cl2 (150 ml) and
treated with a saturated NaHCO3 solution (100 ml).
The aqueous layer was extracted with CH2Cl2 (3×50
ml) and the combined extracts washed successively with
water (30 ml), brine (30 ml) and finally dried over
MgSO4. Evaporation of the solvent furnished an oily
product which was purified by flash column chromatog-
raphy using EA as eluent. The product was finally
recrystallized from diethyl ether to give 8a–e.
H
H
smp), 3.98–4.07 (m, 1H, Hsmp), 7.05–7.13 (m, 4H,
arom). 13C NMR (CDCl3) l (ppm): 21.0 (CH3), 22.6
(CH2), 23.3 (CH2), 27.0 (CH2), 29.4 (CH2), 40.1
(CH2Ar), 50.7 (NCH2), 58.9 (OCH3), 59.4 (NCH), 60.5
(NCH), 75.2 (CH2O), 129.0 (2 CHarom), 129.2 (2
CHarom), 134.8 (Cq), 135.9 (Cq), 174.0 (CꢁO). IR
(CHCl3) cm−1: 2962, 1688, 1515, 1215, 1097. Anal.
calcd for C18H26N2O2 (302) C, 71.49; H, 8.67; N, 9.26.
Found C, 71.69; H, 8.45; N, 9.43.
3.4.5. (2%S,5S)-5-(4-Methoxybenzyl)-2%-methoxymethyl-
[1,1%]bipyrrolidinyl-2-one 10c. Oil; [h]2D5=−38.2 (c 0.97,
1
CHCl3). H NMR (CDCl3) l (ppm): 1.53–1.85 (m, 5H,
3.5.1. (5S)-5-Benzylpyrrolidin-2-one 8a. Mp 57–58°C;
[h]2D5=−38.5 (c 0.80, EtOH). 1H NMR (CDCl3) l
(ppm): 1.71–1.83 (m, 1H, Hpyrrolidine), 2.12–2.26 (m, 3H,
4Hpyrrolidine+1Hsmp), 2.09–2.34 (m, 4H, 3Hsmp+1H
CH2Ar), 3.12–3.21 (m, 1H, Hsmp), 3.28–3.37 (m, 7 H,
OCH3+2Hsmp+NCH+1H CH2Ar), 3.56–3.68 (m, 1H,
Hsmp), 3.76 (s, 3H, OCH3), 3.93–4.04 (m, 1H, Hsmp),
6.81 (d, J=8.5, 2H, Harom), 7.09 (d, J=8.5, 2H, Harom).
13C NMR (CDCl3) l (ppm): 22.6 (CH2), 23.2 (CH2),
27.0 (CH2), 29.6 (CH2), 39.6 (CH2Ar), 50.7 (NCH2),
55.2 (OCH3), 58.9 (OCH3), 59.4 (NCH), 60.6 (NCH),
75.1 (CH2O), 113.9 (2 CHarom), 130.1 (2 CHarom), 158.2
(C-OMe), 174.0 (CꢁO). IR (CHCl3) cm−1: 2952, 1687,
1510, 1245, 1109. Anal. calcd for C18H26N2O3 (318) C,
67.90; H, 8.23; N, 8.80. Found C, 67.80; H, 8.42; N,
8.65.
H
pyrrolidine), 2.75 (d, J=6.4, 2H, CH2Ar), 3.85–3.90 (m,
1H, NCH), 6.87 (brs, 1H, N-H), 7.13–7.25 (m, 5H,
arom). 13C NMR (CDCl3) l (ppm): 26.5 (CH2), 30.2
H
(CH2), 42.7 (CH2Ar), 55.7 (OCH3), 126.7 (CHarom),
128.7 (2 CHarom), 129.1 (2 CHarom), 137.4 (Cq), 178.4
(CꢁO). IR (CHCl3) cm−1: 3430, 1695, 1510, 1216. Anal.
calcd for C11H13NO (175) C, 75.40; H, 7.48; N, 7.99.
Found C, 75.12; H, 7.56; N, 7.86.
3.5.2. (5S)-5-(4-Methylbenzyl)-pyrrolidin-2-one 8b. Mp
80–81°C; [h]2D5=−14.5 (c 1.30, EtOH). 1H NMR
(CDCl3) l (ppm): 1.74–1.84 (m, 1H, Hpyrrolidine), 2.15–
2.24 (m, 3H, Hpyrrolidine), 2.31 (s, 3H, CH3), 2.73 (ddd,
J=13.6, 7.7, 5.8, 2H, CH2Ar), 3.82–3.87 (m, 1H,
NCH), 6.42 (brs, 1H, N-H), 7.04 (d, J=8.1, 2H, Harom),
7.10 (d, J=8.1, 2H, Harom). 13C NMR (CDCl3) l
(ppm): 21.0 (CH3), 26.7 (CH2), 30.1 (CH2), 42.4
(CH2Ar), 55.8 (NCH), 128.9 (2 CHarom), 129.4 (2
CHarom), 134.3 (Cq), 136.3 (Cq), 178.2 (CꢁO). IR
(CHCl3) cm−1: 3426, 1690, 1514, 1215. Anal. calcd for
C12H15NO (189) C, 76.16; H, 7.99; N, 7.40. Found C,
76.27; H, 7.85; N, 7.51.
3.4.6.
(2%S,5S)-5-(4-Chlorobenzyl)-2%-methoxymethyl-
[1,1%]bipyrrolidinyl-2-one 10d. Oil; [h]2D5=−66.6 (c 1.02,
1
CHCl3). H NMR (CDCl3) l (ppm): 1.51–1.88 (m, 5H,
4Hpyrrolidine+1Hsmp), 1.99–2.35 (m, 4H, 3Hsmp+1H
CH2Ar), 3.13–3.17 (m, 1H, Hsmp), 3.24–3.33 (m, 7H,
OCH3+2Hsmp+NCH+1H CH2Ar), 3.59–3.64 (m, 1H,
Hsmp), 3.98–4.04 (m, 1H, Hsmp), 7.09 (d, J=8.3, 2H,
Harom), 7.21 (d, J=8.3, 2H, Harom). 13C NMR (CDCl3)
l (ppm): 22.6 (CH2), 23.3 (CH2), 27.0 (CH2), 29.3
(CH2), 39.8 (CH2Ar), 50.6 (NCH2), 58.9 (OCH3), 59.4
(NCH), 60.3 (NCH), 75.0 (CH2O), 128.6 (2 CHarom),
130.4 (2 CHarom), 132.2 (Cq), 136.5 (C-Cl), 173.8 (CꢁO).
IR (CHCl3) cm−1: 2930, 1688, 1513, 1215, 1102. Anal.
calcd for C17H23ClN2O2 (322) C, 63.25; H, 7.18; N,
8.68. Found C, 63.08; H, 7.32; N, 8.89.
3.5.3. (5S)-5-(4-Methoxybenzyl)-pyrrolidin-2-one 8c. Mp
77–78°C; [h]2D5=−30.2 (c 1.10, EtOH). 1H NMR
(CDCl3) l (ppm): 1.74–1.88 (m, 1H, Hpyrrolidine), 2.15–