Efrosini Barbayianni et al.
FULL PAPERS
(S)-2-Benzyloxycarbonylaminopentanedioic acid 5-tert-
butyl ester 1-(2-methoxyethyl ester (2): White solid; yield:
75%; mp 44–478C; [a]D: +3.3 (c 1.0, CHCl3); 1H NMR
(200 MHz, CDCl3): d=7.37–7.29 (m, 5H), 5.49 (d, J=
8.2 Hz, 1H), 5.10 (s, 2H), 4.48–4.36 (m, 1H), 4.34–4.20 (t,
J=4.4 Hz, 2H), 3.58 (t, J=4.4 Hz, 2H), 3.36 (s, 3H), 2.39–
2.27 (m, 2H), 2.23–2.08 (m, 1H), 2.05–1.85 (m, 1H), 1.43 (s,
9H); 13C NMR (50 MHz, CDCl3): d=172.1, 171.9, 155.8,
136.1, 128.4, 128.1, 128.0, 80.7, 70.1, 66.9, 64.3, 58.9, 53.4,
31.3, 28.0, 27.5; anal. calcd. for C20H29NO7: C 60.74, H 7.39,
N 3.54; found: C 60.53, H 7.51, N 3.45.
General Procedure for the Synthesis of Substrates
To a stirring solution of the appropriate acid (1 mmol) and
the appropriate alcohol (3 mmol) in CH2Cl2 (2 mL), 4-(di-
methylamino)pyridine (0.01 g, 0.1 mmol) and subsequently
N,N’-dicyclohexylcarbodiimide (0.25 g, 1.2 mmol) were
added at 08C. The reaction mixture was stirred for 1 h at
08C and overnight at room temperature. After filtration, the
solvent was evaporated under reduced pressure and EtOAc
(20 mL) was added. The organic layer was washed consecu-
tively with brine, 1N HCl, brine, 5% NaHCO3, and brine,
dried over Na2SO4 and evaporated under reduced pressure.
The residue was purified by column chromatography eluting
with CHCl3 or various mixtures of petroleum ether (40–
608C)/EtOAc.
(S)-2-Benzyloxycarbonylaminopentanedioic acid 1-ethyl
ester 5-(2-methoxyethyl) ester (3a): Oil; yield: 54%; [a]D:
1
+8.0 (c 2.0, CHCl3); H NMR (200 MHz, CDCl3): d=7.38–
7.06 (m, 5H), 5.55 (d, J=8.0 Hz, 1H), 5.06 (s, 2H), 4.40–
4.29 (m, 1H), 4.20–4.05 (m, 4H), 3.52 (d, J=4.6 Hz, 2H),
3.33 (s, 3H), 2.46–1.84 (m, 4H), 1.22 (t, J=7.0 Hz, 3H);
13C NMR (50 MHz, CDCl3): d=172.9, 172.1, 156.2, 136.4,
128.7, 128.4, 128.3, 70.5, 67.2, 63.9, 61.9, 59.2, 53.6, 30.3, 27.8,
14.3; anal. calcd. for C18H25NO7: C 58.84, H 6.86, N 3.81;
found: C 58.60, H 6.98, N 3.68.
4-Benzyloxycarbonylamino-butyric acid propyl ester (1b):
1
Oil; yield: 76%; H NMR (200 MHz, CDCl3): d=7.38–7.21
(m, 5H), 5.08–4.94 (m, 3H), 4.00 (t, J=6.6 Hz, 2H), 3.21
(m, 2H), 2.33 (t, J=7.0 Hz, 2H), 1.88–1.73 (m, 2H), 1.71–
1.52 (m, 2H), 0.90 (t, J=7.2 Hz, 3H); 13C NMR (50 MHz,
CDCl3): d=173.5, 156.7, 136.8, 128.7, 128.6, 128.3, 66.8, 66.4,
40.7, 31.7, 25.4, 22.1, 10.6; MS (ESI): m/z (%)=302 (100)
[M+Na]+; anal. calcd. for C15H21NO4: C 64.50, H 7.58, N
5.01; found: C 64.28, H 7.71, N 4.89.
(S)-2-Benzyloxycarbonylaminopentanedioic acid 5-ethyl
ester 1-(2-methoxyethyl) ester (3b): Oil; yield: 68%; [a]D:
1
+5.4 (c 1.0, CHCl3); H NMR (200 MHz, CDCl3): d=7.39–
4-Benzyloxycarbonylaminobutyric acid butyl ester (1c):
7.24 (m, 5H), 5.60 (d, J=8.0 Hz, 1H), 5.09 (s, 2H), 4.48–
4.34 (m, 1H), 4.32–4.19 (t, J=4.8 Hz, 2H), 4.09 (q, J=
7.4 Hz, 2H), 3.56 (t, J=4.8 Hz, 2H), 3.34 (s, 3H), 2.45–2.30
(m, 2H), 2.28–2.10 (m, 1H), 2.08–1.87 (m, 1H), 1.22 (t, J=
7.0 Hz, 3H); 13C NMR (50 MHz, CDCl3): d=172.6, 171.7,
155.8, 136.1, 128.4, 128.0, 127.9, 70.0, 66.8, 64.2, 60.5, 58.7,
53.3, 30.0, 27.4, 14.0; anal. calcd. for C18H25NO7: C 58.84, H
6.86, N 3.81; found: C 58.63, H 7.04, N 3.69.
1
Oil; yield: 29%; H NMR (200 MHz, CDCl3): d=7.37–7.18
(m, 5H), 5.11–4.91 (m, 3H), 4.03 (t, J=6.6 Hz, 2H), 3.19
(m, 2H), 2.31 (t, J=7.4 Hz, 2H), 1.86–1.72 (m, 2H), 1.64–
1.50 (m, 2H), 1.42–1.24 (m, 2H), 0.90 (t, J=7.0 Hz, 3H);
13C NMR (50 MHz, CDCl3): d=173.5, 156.7, 136.8, 128.6,
128.5, 128.2, 66.8, 64.6, 40.7, 31.7, 30.8, 25.4, 19.3, 13.9; MS
(ESI): m/z (%)=316 (100) [M+Na]+; anal. calcd. for
C16H23NO4: C 65.51, H 7.90, N 4.77; found: C 65.34, H 8.03,
N 4.65.
(S)-2-Benzyloxycarbonylaminopentanedioic acid 1-ethyl
ester 5-propyl ester (3e): Oil; yield: 64%; [a]D: +7.8 (c 1.0,
4-Benzyloxycarbonylaminobutyric acid pentyl ester (1d):
1
CHCl3); H NMR (200 MHz, CDCl3): d=7.39–7.29 (m, 5H),
1
Oil; yield: 50%; H NMR (200 MHz, CDCl3): d=7.38–7.21
5.46 (d, J=7.8 Hz, 1H), 5.11 (s, 2H), 4.45–4.31 (m, 1H),
4.20 (q, J=7.2 Hz, 2H), 4.02 (t, J=7.0 Hz, 2H), 2.47–2.33
(m, 2H), 2.31–2.11 (m, 1H), 2.09–1.89 (m, 1H), 1.74–1.55
(m, 2H), 1.28 (t, J=7.0 Hz, 3H), 0.93 (t, J=7.2 Hz, 3H);
13C NMR (50 MHz, CDCl3): d=172.6, 171.8, 155.8, 136.1,
128.4, 128.0, 127.9, 66.8, 66.2, 61.5, 53.3, 30.1, 27.5, 21.8, 14.0,
10.2; anal. calcd. for C18H25NO6: C 61.52, H 7.17, N 3.99;
found: C 61.28, H 7.34, N 3.81.
(m, 5H), 5.17–4.97 (m, 3H), 4.02 (t, J=6.6 Hz, 2H), 3.20
(m, 2H), 2.31 (t, J=7.2 Hz, 2H), 1.83–1.71 (m, 2H), 1.61–
1.42 (m, 2H), 1.32–1.24 (m, 4H), 0.88 (t, J=6.6 Hz, 3H);
13C NMR (50 MHz, CDCl3): d=173.2, 156.3, 136.8, 128.3,
128.0, 127.9, 66.4, 64.6, 40.3, 31.4, 28.1, 27.9, 25.0, 22.2, 13.8;
MS (ESI): m/z (%)=330 (100) [M+Na]+; anal. calcd. for
C17H25NO4: C 66.43, H 8.20, N 4.56; found: C 66.21, H 8.37,
N 4.39.
(S)-2-Benzyloxycarbonylaminopentanedioic acid 5-ethyl
ester 1-propyl ester (3f): Oil; yield: 71%; [a]D: +6.7 (c 1.0,
4-Benzyloxycarbonylaminobutyric acid hexyl ester (1e):
1
1
Oil; yield: 49%; H NMR (200 MHz, CDCl3): d=7.38–7.19
CHCl3); H NMR (200 MHz, CDCl3): d=7.37–7.28 (m, 5H),
(m, 5H), 5.22 (m, 1H), 5.06 (s, 2H), 4.00 (t, J=6.6 Hz, 2H),
3.18 (m, 2H), 2.29 (t, J=7.4 Hz, 2H), 1.84–1.70 (m, 2H),
1.55–1.43 (m, 2H), 1.40–1.16 (m, 6H), 0.84 (t, J=6.0 Hz,
3H); 13C NMR (50 MHz, CDCl3): d=173.7, 156.8, 136.8,
128.6, 128.5, 128.2, 66.8, 64.9, 40.6, 31.7, 31.6, 28.7, 25.7, 25.4,
22.8, 14.1; MS (ESI) m/z (%)=344 (100) [M+Na]+; anal.
calcd. for C18H27NO4: C 67.26, H 8.47, N 4.36; found: C
66.98, H 8.62, N 4.18.
5.55 (d, J=8.0 Hz, 1H), 5.10 (s, 2H), 4.46–4.31 (m, 1H),
4.17–4.02 (m, 4H), 2.48–2.34 (m, 2H), 2.31–2.10 (m, 1H),
2.08–1.85 (m, 1H), 1.77–1.58 (m, 2H), 1.23 (t, J=7.4 Hz,
3H), 0.93 (t, J=7.4 Hz, 3H); 13C NMR (50 MHz, CDCl3):
d=172.6, 171.9, 155.9, 136.1, 128.4, 128.1, 128.0, 67.1, 66.9,
60.6, 53.3, 30.1, 27.6, 21.7, 14.1, 10.2; anal. calcd. for
C18H25NO6: C 61.52, H 7.17, N 3.99; found: C 61.35, H 7.31,
N 3.85.
4-Benzyloxycarbonylaminobutyric acid 2-methoxyethyl
ester (1f): White low melting point solid-syrup; yield: 73%;
1H NMR (200 MHz, CDCl3): d=7.38–7.08 (m, 5H), 5.12–
4.98 (m, 3H), 4.19 (t, J=4.8 Hz, 2H), 3.54 (t, J=4.8 Hz,
2H), 3.34 (s, 3H), 3.21 [q (ap), J=6.6 Hz, 2H], 2.37 (t, J=
7.2 Hz, 2H), 1.89–1.71 (m, 2H); 13C NMR (50 MHz,
CDCl3): d=173.4, 156.7, 136.8, 128.7, 128.6, 128.3, 70.6, 66.8,
63.7, 59.1, 40.5, 31.6, 25.3; anal. calcd. for C15H21NO5: C
61.00, H 7.17, N 4.74; found: C 60.78, H 7.33, N 4.62.
(S)-2-Benzyloxycarbonylaminopentanedioic Acid 1-
Allyl Ester 5-Ethyl Ester (3d)
A
mixture of Z-GluACHTNGUTERNNU(G OEt)-OH (0.31 g, 1.0 mmol) and
Cs2CO3 (0.16 g, 0.5 mmol) was dissolved in DMF (5 mL)
and a few drops of water were added. The mixture was dis-
tilled under reduced pressure to dryness and the residue re-
2330
ꢀ 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2009, 351, 2325 – 2332