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M. J. Fray et al. / Tetrahedron 62 (2006) 6869–6875
2H), 3.47 (m, 5H), 3.62 (t, J 6 Hz, 2H), 4.55 (s, 2H), 6.99
(m, 1H), 7.10 (m, 2H); LRMS: m/z (ESþ) 335 [MHþ],
357 [MNaþ]. Found: C, 66.74; H, 8.88; N, 8.20,
C19H30N2O3$0.4H2O requires C, 66.79; H, 9.09; N, 8.20%.
2H), 3.61 (s, 2H), 4.02 (m, 1H), 4.6–4.7 (br s, 4H), 7.1–7.2
(br, 3H); LRMS: m/z (ESþ) 319 [MHþ], 341 [MNaþ].
Amine 13d: yellow oil; dH (CDCl3, 400 MHz) 1.48 (s, 9H),
1.8 (br, 1H), 2.05 (m, 1H), 2.52 (br, 2H), 2.64 (m, 1H), 2.75
(br, 1H), 3.25 (s, 3H), 3.61 (s, 2H), 3.91 (br, 1H), 4.6–4.7 (br
s, 4H), 7.1–7.25 (br, 3H); LRMS: m/z (ESþ) 333 [MHþ], 355
[MNaþ].
Amine 7d: colourless oil; dH (CDCl3, 400 MHz) 1.50 (s,
9H), 2.43 (m, 4H), 2.93 (t, J 5 Hz, 2H), 3.44 (s, 2H), 3.67
(m, 6H), 4.58 (s, 2H), 7.03 (m, 1H), 7.12 (m, 2H); LRMS:
m/z (ESþ) 333 [MHþ], 355 [MNaþ].
2.3. Deprotection of N-Boc derivatives (7a–j and 13a–d):
general methods
Amine 7e: colourless oil; dH (CDCl3, 400 MHz) 1.47 (s, 9H),
1.56 (m, 2H), 1.84 (br, 2H), 2.13 (m, 2H), 2.68 (br, 2H), 2.90
(t, J 6 Hz, 2H), 3.20 (m, 1H), 3.31 (s, 3H), 3.41 (s, 2H), 3.62
(m, 2H), 4.56 (s, 2H), 7.00 (m, 1H), 7.10 (m, 2H). Found: C,
69.64; H, 8.94; N, 7.72, C21H32N2O3 requires C, 66.97; H,
8.95; N, 7.77%.
Hydrogen chloride was bubbled through an ice-cooled solu-
tion of the Boc-protected amine (7a–j or 13a–d) in dichloro-
methane (10–12 mL/g) for 20 min. The solution was then
stirred for a further 30 min at room temperature and evapo-
rated under reduced pressure to afford 1 or 2 (hydrochlo-
ride). Alternatively, a solution of the Boc-protected amine
in dichloromethane (10–12 mL/g) was treated with an equal
volume of trifluoroacetic acid and the solution stirred at
room temperature for 2 h. Removal of the solvents under re-
duced pressure gave 1 or 2 (trifluoroacetate). Spectroscopic
data for the amines 1a–j and 2a–d are given below.
Amine 7f: pale pink oil; dH (CDCl3, 400 MHz) 1.48 (s, 9H),
1.77 (m, 1H), 2.02 (m, 1H), 2.5 (m, 2H), 2.61 (m, 1H), 2.77
(m, 1H), 2.88 (t, J 6 Hz, 2H), 3.25 (s, 3H), 3.56 (s, 2H), 3.62
(t, J 6 Hz, 2H), 3.90 (m, 1H), 4.55 (s, 2H), 6.99 (d, J 8 Hz,
1H), 7.08–7.18 (m, 2H); LRMS: m/z (ESþ) 347 [MHþ].
Found: C, 68.68; H, 8.73; N, 8.04, C20H30N2O3$0.16H2O
requires C, 68.76; H, 8.74; N, 8.02%.
Amine 1a$HCl: colourless foam; dH (DMSO-d6, 400 MHz)
2.50 (s, 6H), 3.15 (t, J 6 Hz, 2H), 3.35 (br, 2H), 4.26 (m, 4H),
7.30 (m, 2H), 7.55 (d, J 8 Hz, 1H), 9.55 (br, 2H); LRMS: m/z
(ESþ) 191 [MHþ], 213 [MNaþ]. Found: C, 47.24; H, 7.14;
N, 8.49, C12H18N2$HCl$H2O$CH2Cl2 requires C, 47.36;
H, 7.03; N, 8.50%.
Amine 7g: colourless oil; dH (CDCl3, 400 MHz) 1.48 (s,
9H), 1.76 (m, 1H), 2.02 (m, 1H), 2.5 (m, 2H), 2.61 (m,
1H), 2.77 (m, 1H), 2.88 (t, J 6 Hz, 2H), 3.25 (s, 3H), 3.56
(s, 2H), 3.62 (t, J 6 Hz, 2H), 3.90 (m, 1H), 4.55 (s, 2H),
6.99 (d, 1H), 7.10 (t, J 8 Hz, 1H), 7.16 (d, J 8 Hz, 1H);
LRMS: m/z (ESþ) 347 [MHþ], 369 [MNaþ]. Found: C,
68.71; H, 8.71; N, 7.86, C20H30N2O3$0.1H2O requires C,
68.97; H, 8.74; N, 8.04%.
Amine 1b$2HCl: colourless foam; dH (DMSO-d6, 400 MHz)
3.06 (t, J 6 Hz, 2H), 3.14 (t, J 6 Hz, 2H), 3.30 (s, 3H), 3.35 (t,
J 6 Hz, 2H), 3.67 (t, J 6 Hz, 2H), 4.13 (s, 2H), 4.25 (s, 2H),
7.25 (d, J 6 Hz, 1H), 7.32 (t, J 6 Hz, 1H), 7.50 (d, J 6 Hz,
1H); LRMS: m/z (ESþ) 221 [MHþ], 243 [MNaþ]. Found:
C, 50.1; H, 7.68; N, 8.78, C13H20N2O$2HCl$H2O requires
C, 50.17; H, 7.77; N, 9.00%.
Amine 7h: oil; dH (CDCl3, 400 MHz) 1.48 (s, 9H), 1.69 (d,
J 10 Hz, 1H), 1.85 (d, J 10 Hz, 1H), 2.57 (d, J 10 Hz, 1H),
2.83 (d, J 10 Hz, 1H), 2.90 (t, J 6 Hz, 2H), 3.38 (s, 1H),
3.63 (t, J 6 Hz, 3H), 3.70 (d, J 2 Hz, 2H), 4.08 (d, J 6 Hz,
1H), 4.4 (s, 1H), 4.6 (s, 1H), 7.00 (d, J 6 Hz, 1H), 7.08–7.2
(m, 2H); LRMS: m/z (ESþ) 345 [MHþ], 367 [MNaþ].
Amine 1c: free base, pale yellow gum; dH (CDCl3, 400 MHz)
2.23 (s, 3H), 2.6 (t, J 5 Hz, 2H), 2.82 (t, J 5 Hz, 2H), 3.16 (t,
J 5 Hz, 2H), 3.32 (s, 3H), 3.47 (s, 2H), 3.50 (t, J 5 Hz, 2H),
4.01 (s, 2H), 6.9 (d, J 8 Hz, 1H), 7.06 (t, J 8 Hz, 1H), 7.13
(d, J 8 Hz, 1H); LRMS: m/z (ESþ) 235 [MHþ]. Found: C,
70.6; H, 9.56; N, 11.76, C14H22N2O$0.2H2O requires C,
70.67; H, 9.49; N, 11.77%.
Amine 7i: colourless oil; dH (CDCl3, 400 MHz) 1.45 (s, 9H),
2.81 (t, J 6 Hz, 2H), 2.95 (t, J 6 Hz, 2H), 3.22 (s, 3H), 3.60
(m, 6H), 4.01 (m, 1H), 4.58 (s, 2H), 7.00 (m, 1H), 7.13 (m,
2H); LRMS: m/z (ESþ) 333.3 [MHþ], 355 [MNaþ].
Amine 7j: colourless oil; dH (CDCl3, 400 MHz) 1.46 (s, 3H),
1.48 (s, 9H), 2.82 (t, J 6 Hz, 2H), 3.03 (d, J 6 Hz, 2H), 3.18
(s, 3H), 3.20 (m, 2H), 3.59 (s, 2H), 3.63 (t, J 6 Hz, 2H), 4.56
(s, 2H), 7.00 (br, 1H), 7.14 (m, 2H); LRMS: m/z (ESþ) 347
[MHþ], 369 [MNaþ].
Amine 1d$2HCl, colourless solid; dH (DMSO-d6, 400 MHz)
3.20 (m, 4H), 3.37 (m, 2H), 3.62 (m, 2H), 3.90 (m, 4H), 4.22
(m, 2H), 4.32 (s, 2H), 7.30 (m, 2H), 7.62 (m, 1H), 9.58 (br s,
2H), 11.40 (br s, 1H); LRMS: m/z (ESþ) 233 [MHþ].
Amine 13a: white waxy solid; dH (CDCl3, 400 MHz) 1.48 (s,
9H), 2.42 (m, 4H), 3.48 (s, 2H), 3.68 (m, 4H), 4.65 (br, 4H),
7.20 (br m, 2H); LRMS: m/z (ESþ) 319 [MHþ], 341 [MNaþ].
Amine 1e: free base, gum; dH (CDCl3, 400 MHz) 1.56 (m,
2H), 1.86 (br, 2H), 2.16 (dt, J 10 and 3 Hz, 2H), 2.69 (br,
2H), 2.82 (t, J 6 Hz, 2H), 3.15 (t, J 6 Hz, 2H), 3.20 (m,
1H), 3.32 (s, 3H), 3.39 (s, 2H), 4.01 (s, 2H), 6.90 (d,
J 7 Hz, 1H), 7.03 (t, J 7 Hz, 1H), 7.10 (d, J 7 Hz, 1H).
Found C, 72.88; H, 9.29; N, 10.69, C16H24N2O$0.3H2O
requires C, 72.80; H, 9.32; N, 10.61%.
Amine 13b: yellow oil; dH (CDCl3, 400 MHz) 1.48 (s, 9H),
2.24 (s, 3H), 2.39 (t, J 6 Hz, 2H), 3.31 (s, 2H), 3.49 (t, J 6 Hz,
2H), 3.53 (s, 3H), 4.55–4.7 (br s, 4H), 7.06–7.35 (br m, 3H);
LRMS: m/z (ESþ) 321 [MHþ], 343 [MNaþ].
Amine 1f$2HCl: colourless foam; dH (CDCl3, 400 MHz)
2.23 (br, 2H), 3.17 (br, 2H), 3.35 (s, 3H), 3.40 (br, 2H),
3.50 (br, 2H), 3.75 (m, 2H), 4.13 (br, 1H), 4.32 (br, 2H),
Amine 13c: colourless oil; dH (CDCl3, 400 MHz) 1.48 (s,
9H), 2.95 (t, J 6 Hz, 2H), 3.23 (s, 3H), 3.57 (t, J 6 Hz,