Synthesis and characterization of linear and cyclic ... - EleA@UniSA

Tert-butyl 6-aminohexanoate (91):
To a solution of 90 (1.95 g, 6.07 mmol) in dry MeOH (150 mL), acetic acid (1.39 mL, 24.0 mmol)
and palladium on charcoal (10% w/w, 0.19 g) were added. The reaction mixture was stirred under a
hydrogen atmosphere at room temperature for 1 h and filtered through celite. The solvent was
evaporated in vacuo to give crude 91 (1.13 g, 100%, colorless oil) which was used in the next step
without purification; Rf (95/5, CH2Cl2/CH3OH) 0.46; H (400.13 MHz CDC13) 1.33 (2H, q, J 6.5 Hz,
CH2CH2CH2COOt-Bu), 1.39 (9H, s, COOC(CH3)3), 1.55 (2H, q, J 6.5 Hz, CH2CH2CH2CH2CH2NH),
1.62 (2H, q, J 6.5 Hz, CH2CH2CH2COOt-Bu), 2.17 (2H, t, J 6.5 Hz, CH2CH2CH2COOt-Bu), 2.84 (2H, t,
J 6.5 Hz, CH2CH2CH2NH); C (75.50 MHz, CDCl3) 24.3, 25.8, 27.2, 28.0, 35.1, 39.4, 80.2, 177.2; m/z
(ES) 188 (MH + ); (HRES) MH + , found 188.1647. C10H22NO2 + requires 188.1651.
Benzyl 2-hydroxyethylcarbamate (93):
To a solution of ethanolamine (92, 2.00 g, 32.8 mmol) in dry CH2Cl2 (30 mL) at 0°C, a solution Cbz-
Cl (3.73 mL, 26.2 mmol) in dry CH2Cl2 (20 mL) was slowly added. The reaction mixture was stirred for
2 hours at 0°C and at room temperature overnight. The resulting mixture was washed with an aqueous
saturated solution of NaHCO3 and the aqueous phase extracted with CH2Cl2. (three times). The organic
phase was dried over MgSO4, filtered and the solvent evaporated in vacuo to give crude 93 (5.11 g,
100%, yellow pale oil) which was used in the next step without purification; Rf (92/8, CH2Cl2/CH3OH)
0.47; H (250.13 MHz CDC13) 3.36 (2H, br t, J 6.5 Hz, CH2OH), 3.71 (2H, q, J 6.5 Hz, CH2NH), 5.11
(2H, s, CH2Bn), 7.35 (5H, m, Ar.); C (62.89 MHz, CDCl3) 43.3, 61.7, 66.7, 127.9, 128.0, 128.4, 136.2,
157.0; m/z (ES) 196 (MH + ); (HRES) MH + , found 196.0970. C10H14NO3 + requires 196.0974.
Benzyl 2-iodoethylcarbamate (94):
To a solution of PPh3 (2.66 g, 10.2 mmol) in CH2Cl2 (10 mL), I2 (2.59 g, 10.2 mmol) in CH2Cl2 (10
mL) was slowly added. The reaction mixture was stirred for 30 min. Imidazole (1.39 g, 20.4 mmol) in
CH2Cl2 (10 mL) was then added and the reaction mixture was stirred for further 30 min. Finally, 93
(1.00 g, 5.13 mmol) was added and the reaction mixture stirred for 3 hours. The resulting mixture was
washed with an aqueous saturated solution of NaHCO3 and 10 %w/w of Na2S2O3 and the aqueous phase
extracted with CH2Cl2 (three times). The organic phase was dried over MgSO4, filtered and the solvent
evaporated in vacuo to give a crude material, which was purified by flash chromatography
(AcOEt/petroleum ether, from: 0/100 to 100/0) to give 94 (1.20 g, 77%) as white amorphous solid;
[Found: C, 39.4; H, 4.0. C10H12INO2 requires C, 39.36; H, 3.96%]; Rf (6/4, AcOEt/petroleum ether)
0.88;H (250.13 MHz CDC13) 3.25 (2H, t, J 6.5 Hz, CH2I), 3.55 (2H, q, J 6.5 Hz, CH2NH), 5.11 (2H,
s, CH2Bn), 7.36 (5H, m, Ar.); C (62.89 MHz, CDCl3) 5.1, 43.0, 66.5, 127.8, 128.1, 128.2, 136.0, 155.8;
m/z (ES) 306 (MH + ); (HRES) MH + , found 305.9989. C10H13INO2 + requires 305.9991.
Benzyl 2-(5-(tert-butoxycarbonyl)pentylamino) ethylcarbamate (95):
To a solution of 91 (0.35 g, 1.87 mmol) in dry acetonitrile (10 mL), at reflux, K2CO3 (0.88 g, 6.38
mmol) was added. The reaction mixture was stirred for 10 min. After that, a solution of 94 (0.40 g, 1.31
mmol) in dry acetonitrile (5 mL), was added and the reaction mixture was stirred at reflux overnight.
The product was filtered and the crude was purified by flash column chromatograph, (CH2Cl2/CH3OH,
from: 100/0 to 90/10) to give 95 (0.32 g, 67%) as yellow light oil; [Found: C, 65.9; H, 8.6. C20H32N2O4
requires C, 65.91; H, 8.62%]; Rf (93/7, CH2Cl2/CH3OH) 0.71;H (300.10 MHz CDC13) 1.35 (2H, q, J
6.5 Hz, CH2CH2CH2CH2CH2NH), 1.43 (9H, s, COOC(CH3)3), 1.57 (2H, q, J 6.0 Hz,
CH2CH2CH2CH2CH2NH), 1.67 (2H, q, J 6.0 Hz, CH2CH2CH2CH2CH2NH), 2.21 (2H, t, J 6.0 Hz,
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