1088
M. Cal et al.
334.05; calculated for (C9H11F6NO4 ? Na)? 334.05. H
NMR (500 MHz, CDCl3): d = 1.84 ppm (m, J = 7.06 Hz,
2H); 2.43 ppm (t, J = 7.30 Hz, 2H); 3.23 ppm (q,
3 J = 6.57 Hz, 2H); 4.38–4.44 ppm (m, 3 Hz, 4H);
5.40 ppm (broad signal, 1H). 1H NMR (500 MHz, DMSO-
d6): d = 1.73 ppm (m, J = 7.18 Hz, 2H); 2.44 ppm (t,
J = 7.46 Hz, 2H); 3. 06 ppm (q, J = 6.01 Hz, 2H);
4.62 ppm (q, J = 9.12 Hz); 7.65 ppm (broad signal, 1H).
3-({[(4-Methoxybenzyl)oxy]carbonyl}amino)propanoic
acid (5a). mp = 79–81 °C. ESI–MS: Found: 252.09; cal-
3.48 ppm (m, 2H); 5.07 ppm (s, 2H); 5.28-542 ppm (broad
signal, 0.89H); 6.18–6.30 ppm (broad signal, 0.11H);
7.28 ppm (d, 3 J = 8.40 Hz, 2H); 7.33 ppm (d, J =
1
1
8.40 Hz, 2H). H NMR (500 MHz, DMSO-d6): d = 2.37
ppm (t, J = 6.76 Hz, 2H); 3.19 ppm (q, J = 6.28,
3 J = 6.18, 2H); 4.98 ppm (s, 2H); 7.31 ppm (t,
J = 6.18 Hz, 1H); 7.36 ppm (d, J = 7.39 Hz, 2H);
7.41 ppm (d, J = 7.41 Hz, 2H).
4-({[(4-Chlorobenzyl)oxy]carbonyl}amino)butanoic
acid (4b). mp = 100° C. ESI–MS: Found: 270.05; calculated
for (C12H14ClNO4–H)- 270.06. 1H NMR (500 MHz,
CDCl3): d = 1.86 ppm (m, J = 6.96 Hz, 2H); 2.41 ppm
(t, J = 7.10 Hz, 2H); 3.27 ppm (t, J = 6.75 Hz, 2H);
5.08 ppm (s, 2H); 5.90–5.08 ppm (broad signal, 0.10H);
7.05–7.25 ppm (broad signal, 0.90H); 7.29 ppm (d,
J = 8.40 Hz, 2H); 7.33 ppm (d, J = 8.40 Hz, 2H). 1H NMR
(500 MHz, DMSO-d6): d = 1.52 ppm (m, J = 6.79 Hz,
J = 6.77 Hz, 2H); 2.11 ppm (t, J = 7.02 Hz, 2H); 2.91 ppm
(q, J = 5.73 Hz, 2H); 4.90 ppm (s, 2H); 7.21 ppm (t,
J = 5.90 Hz, 1H); 7.27 ppm (d, J = 7.80 Hz, 2H);
7.32 ppm (d, J = 7.81 Hz, 2H).
1
culated for (C12H15NO5–H)- 252.09. H NMR (500 MHz,
CDCl3): d = 2.56 ppm (t, J = 2 Hz, 2H); 3.42 ppm (mul-
tiplet, 2H); 3.78 ppm (s, 3H); 5.00 ppm (s, 0.56H); 5.06 ppm
(s, 1.44H); 5.28 ppm (s, 0.72H); 6.29 ppm (s, 0.28H);
6.85 ppm (d, J = 7.89 Hz, 2H); 7.26 ppm (d, J = 7.90 Hz,
2H); 8.70–9.65 ppm (broad signal, 1H). 1H NMR (500 MHz,
DMSO-d6): d = 2.34 ppm (t, J = 6.94 Hz, 2H); 3.15 ppm
(quartet, J = 6.60, J = 6.28, 2H); 3.70 ppm (s, 3H);
4.88 ppm (s, 2H); 6.87 ppm (d, J = 8.41 Hz, 2H); 7.16 (t,
J = 6.18 Hz, 1H); 7.24 ppm (d, J = 8.41 Hz, 2H).
4-({[(4-Methoxybenzyl)oxy]carbonyl}amino)butanoic
acid (5b). mp = (liquid at RT). ESI–MS: Found: 266.10;
calculated for (C13H17NO5–H)- 266.09. 1H NMR
(500 MHz, CDCl3): d = 1.94 ppm (m, J = 7.83 Hz,
J = 7.74 Hz, 2H); 2.39 ppm (t, J = 6.33 Hz, 2H); 2.80 ppm
(q, J = 7.48 Hz, 2H); 3.69 ppm (s, 3H); 4.50 ppm (s, 2H);
6.89 ppm (d, J = 7.20 Hz, 2H); 7.36 ppm (d, J = 7.70 Hz,
Results and discussion
b and c dicarboxylic acids may be relatively easily con-
verted to cyclic N-hydroxyimides. These cyclization
products are often used as the additives in peptide synthesis
and for activation of carboxylic group in the modification
of proteins. N-hydroxyimides also react with aromatic and
aliphatic sulfochlorides forming crystalline derivatives
with high yield. In this paper, we tested a new way of
synthesis of N-protected non-proteinaceous amino acids
based on Lossen rearrangement. Reaction of sulfonic ester
of N-hydroxyimide and selected alcohol is carried out in
the presence of triethylamine at 65 °C. As the solvents we
tested pyridine, benzene and the alcohol itself.
1
2H); 5.86 ppm (broad signal, 1H). H NMR (500 MHz,
DMSO-d6): d = 1.72 ppm (m, J = 7.33 Hz, J = 7.54 Hz,
2H); 2.29 ppm (t, J = 7.30 Hz, 2H); 2.77 ppm (q,
J = 7.28 Hz, 2H); 3.63 ppm (s, 3H); 4.57 ppm (s, 2H);
7.09 ppm (d, J = 7.70 Hz, 2H); 7.45 ppm (d, J = 7.75 Hz,
2H); 7.66 ppm (broad signal, 1H).
3-({[(4-Chlorobenzyl)oxy]carbonyl}amino)propanoic
acid (4a). mp = 119–120° C. ESI–MS: Found: 256.04;
calculated for (C12H14ClNO4–H)- 256.04. 1H NMR
(500 MHz, CDCl3): d = 2.61 ppm (t, J = 3 Hz, 2H);
Fig. 2 Scheme of the reaction
of obtaining Na-urethane-
protected b-alanine and
c-aminopropionic acid (GABA)
derivatives
O
OH
O
I
O
1) TsCl or MesCl
2) R-CH2OH / NEt3
N
CH R
2
RCH O
(CH )
2 n
NH
O
2
O
(CH )
2 n
1) 1 M NaOH / MeOH
2) HCl / H2O
O
II
O
CH R
2
HO
(CH )
2 n
NH
O
123