Spirodiamine Templates
3797
tert-Butyl 2-(2-Chloroethyl)-2-cyanopyrrolidine-1-carboxylate (4)
A solution of n-BuLi (2.5 M, 12 ml, 0.03 mol) in THF was added to a
solution of diisopropylamine (5.6 ml, 0.04 mol) in THF (30 ml) under an
N2 atmosphere at 2 788C. After 30 min, compound 3 (4.91 g, 0.025 mol)
was added to the mixture at 2788C. After complete addition, the resulting
mixture was stirred at 2788C for 45 min. 1-Bromo-2-chloro-ethane (4.1 ml,
0.05 mol) was added to the mixture at 2788C. After complete addition, the
mixture was allowed to warm up to room temperature and stirred overnight.
The reaction mixture was quenched by aqueous NH4Cl and extracted with
EtOAc (50 ml ꢀ 3). The combined organic layer was dried over Na2SO4,
filtered, and concentrated under reduced pressure to give crude compound 4
(5.4 g) as a brown liquid. The crude product was purified by silica column
chromatography to afford compound 4 (3.5 g, yield 55%) as a yellow solid.
1H NMR (400 MHz, CDCl3): 3.41–3.95 (m, 4H), 2.21–2.65 (m, 2H), 1.71–
2.35 (m, 4H), 1.50 (s, 9H): MS (m/z): 203 (M-23), 259 (M þ 1).
tert-Butyl 1,7-Diazaspiro[4.4]nonane-1-carboxylate (5)
A solution of compound 4 (1.1 g, 4.4 mmol) in methanol (40 ml) and conc.
.
NH3 H2O (2.8 ml) was stirred with Raney Ni (1 g) under an H2 atmosphere
(30 psi) at 508C for 6 h. After filtrating off Raney Ni, the filtrate was concen-
trated under reduced pressure to give compound 5 (1.0 g, yield 90%). 1H NMR
(400 MHz, CDCl3): 3.20–3.50 (m, 3H), 2.16–2.67 (m, 4H), 1.62–1.89
(m, 5H), 1.49 (s, 9H): 13C NMR (400 MHz, CDCl3): 154.7, 81.1, 67.4,
1
53.7, 47.8, 46.0, 39.8, 36.1, 28.5, 23.2; H-13C HMQC: H3.22, 3.48/C53.7;
H3.23, 2.67/C47.8; H2.16, 2.43/C47.8; H2.23, 1.89/C46.0; H1.76, 1.80/
C36.1; H1.62, 1.70/C23.2; MS (m/z): 227 (M þ 1).
tert-Butyl 2-(3-Chloropropyl)-2-cyanopyrrolidine-1-carboxylate (6)
General procedure for compound 4 was followed to afford the title product. 1H
NMR (400 MHz, CDCl3): 3.31–3.75 (m, 4H), 2.35–2.51 (m, 2H), 1.70–2.25
(m, 6H), 1.51 (s, 9H): MS (m/z): 295 (M þ 23).
tert-Butyl 1,7-Diazaspiro[4.5]decane-1-carboxylate (7)
General procedure for compound 5 was followed to afford the title product. 1H
NMR (400 MHz, CDCl3): 2.80–3.48 (m, 6H), 1.60–2.67 (m, 8H), 1.49
(s, 9H): 13C NMR (400 MHz, CDCl3): 154.3, 80.3, 62.3, 48.3, 43.4, 37.3,
31.4, 28.7, 28.5, 21.8, 20.8; 1H-13C HMQC: H3.48, 3.02/C48.3; H3.15,
2.92/C43.4; H3.20, 2.80/C37.3; H2.67, 2.25/C31.4; H2.05, 1.90/H28.7;
H1.98, 1.85/21.8; H1.65, 1.60/C20.8; MS (m/z): 241 (M þ 1).