S. Mahboobi et al. / Tetrahedron: Asymmetry 9 (1998) 2369–2376
2375
7H), 1.33–1.49 (m; 20 H); FD-MS: m/z=423 [M+·]; anal. calcd for C22H37N3O5 (423.55): C 62.39; H
8.80; N 9.92. Found C 62.08; H 8.59; N 9.79.
3.7. (+)-(3S,4R)-3,4-Bis((2S)-pyrrolidin-2-yl)-2-pyrrolidinonedihydrochloride 9
A solution of 8 (0.10 g, 0.22 mmol) in dry chloroform (2.2 ml) was cooled to 0°C, and trimethylsilyl
iodide (TMSI) (0.17 ml) was added dropwise by a syringe. After 10 min stirring at room temperature
methanol (1.2 ml) was added in one portion. After 5 min all volatile components were removed in vacuo
and the residue was dissolved in diethyl ether (4 ml) and acetic acid (4 ml, 30%). The aqueous layer
was separated, washed with diethyl ether (2×5 ml) and evaporated to dryness in vacuo. The brown
residue was stirred with a mixture of 6 N NaOH (10 ml) and methylene chloride (10 ml) for 12 h. The
organic layer was separated, dried over Na2SO4 and concentrated to dryness. The white residue was
dissolved in diethyl ether (3 ml) and a standard ethereal solution of HCl (2 ml) was added dropwise. The
white precipitate was filtered off and recrystallised from methanol, affording 9-hydrochloride (50.3 mg,
20
0.17 mmol, 75%) as colourless crystals; m.p.: 236–237°C (decomp.); [α] =+44.3 (c=0.79, MeOH);
D
1
IR (KBr): ν (cm−1)=3537, 2761 (NH); 2942 (CH); 1700 (CO); H-NMR (CD3OD, 250 MHz): δ
(ppm)=3.64–3.80 (m; 3H), 3.30–3.42 (m; 5H), 2.74–2.85 (m; 1H), 2.60–2.66 (m; 1H), 2.28–2.45 (m;
2H), 1.66–2.20 (m; 6H); FAB-MS: m/z=224 [M+H]+·; anal. calcd for C12H23Cl2N3O·0.5H2O (305.25):
C 47.22; H 7.90; N 13.77; Found: C 47.23; H 7.20; N 13.79.
3.8. (−)-1-Methyl-(3S,4R)-3,4-bis((2S)-N-(tert-butyloxycarbonyl)pyrrolidin-2-yl)-2-pyrrolidinone 10
Compound 8 (0.30 g, 0.71 mmol) was dissolved in dry THF (30 ml), NaH (27.5 mg, 0.92 mmol,
80% suspension in oil) was added, and the mixture was refluxed for 1 h. After cooling to room
temperature methyl iodide (8.80 ml, 0.14 mol) was added, and the mixture was refluxed for 1 h.
After cooling, water (5 ml) was added carefully. The organic layer was separated and the aqueous
layer was extracted with diethyl ether (50 ml). The combined organic layers were dried over Na2SO4
and the solvent was removed under reduced pressure. The resulting brown residue was purified by
column chromatography (ethyl acetate:hexane=1:1) and the product was recrystallised from diethyl ether,
yielding the N-methylpyrrolidinone 10 (0.25 g, 0.57 mmol, 80%) as colourless, cubic crystals; m.p.
20
143–145°C; [α] =−113.4 (c=1.7, MeOH); IR (KBr): ν (cm−1)=2975, 2934, 2884 (CH); 1690 (CO);
D
1H-NMR (CDCl3, 400 MHz): δ (ppm)=3.70–4.30 (m; 4H), 3.07–3.70 (m; 7H), 2.83 (s; 3H, N–CH3),
1.65–2.33 (m; 10H), 1.49 (s; 15H); FD-MS: m/z=437 [M+·]; anal. calcd for C23H39N3O5 (437.58): C
63.13; H 8.98; N 9.60. Found: C 63.17; H 8.97; N 9.42.
References
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