2306
L. Ambroise et al.
FEATURE ARTICLE
Purification by flash chromatography (petroleum ether–EtOAc,
IR (KBr): 3279, 1784, 1706, 1700 cm–1.
5:1) gave the N,N diprotected , -diamino acid derivative 32.
1H NMR (500 MHz, DMSO-d6): = 1.30 (3 H, d, J = 6.5), 2.48 (3
H, s), 4.45 (1 H, t, J = 7), 4.50 (1 H, dq, J = 9.5, 6.5), 4.59 (1 H, dd,
J = 10.5, 7), 4.60 (1 H, dd, J = 10.5, 7), 4.78 (1 H, dd, J = 9.5, 1.5),
7.39–7.46 (4 H, m), 7.47 (2 H, td, J = 7.5, 1), 7.56 (2 H, t, J = 7.5),
7.95 (1 H, d, J = 7.5), 8.01 (1 H, d, J = 7.5), 8.02 (2 H, d, J = 7.5),
8.41 (1 H, br s).
13C NMR (125 MHz, DMSO-d6): = 14.7, 21.3, 46.7, 53.4, 61.3,
68.4, 119.9, 122.2, 125.2, 127.3, 127.9, 130.3, 134.4, 140.5, 141.3,
143.4, 151.2, 154.4, 196.3.
Hydrolysis of the Thioester
Aq H2O2 (30% w/w, 45 L, 0.4 mmol, 4 equiv) was added dropwise
at 0 °C to a solution of the thioester 32 (0.1 mmol) in THF (5 mL)
and the resulting solution was stirred for 15 min at 0 °C. Aq NaOH
(0.22 M, 1.4 mL, 0.3 mmol, 3 equiv) was added dropwise and the
reaction stirred for 1 h at r.t. The solvent was removed under re-
duced pressure and the residue taken up in H2O (15 mL) and Et2O
(15mL). The organic layer was removed and the aqueous layer ex-
tracted with Et2O (2 10 mL). The aqueous layer was carefully
acidified to pH 3 with 1 M HCl and extracted with EtOAc. The com-
bined EtOAc extracts were dried (MgSO4), filtered and the solvent
removed under reduced pressure to give the crude acid 33 as a white
solid.
MS (EI): m/z (%) = 473 (MH+, 0.1), 472 (0.1), 414 (0.1), 367 (0.3),
279 (30), 265 (0.2), 178 (100).
HRMS: m/z calcd for C27H24N2O4S, 472.1457. Found: 472.1435.
(4S,5S)-5–Methyl-4-(4 -tolylthiocarbonyl)-2-oxo-1-(N-fluoren-
9-yl-methyloxycarbonyl) Imidazolidinone (34)
The imidazolidinone 34 was prepared from the monoprotected di-
amine 30a, using the same procedure employed to prepare 26 from
the -amino thioester 24.
Table 2 1H and 13C NMR Data for Compounds 29, 32, 33 and 35
H (500 MHz, CDCl3)
C (125 MHz, CDCl3)
29a
1.32 (3 H, d, J = 6.5) 2.03 (3 H, s), 4.19 (1 H, t, J = 6.5), 4.44 (2 H, d, 20.0, 21.1, 47.1, 47.3, 67.7, 119.9, 124.9, 127.0,
J = 6.5), 4.90–4.92 (1 H, m), 5.06 (1 H, d, J = 7), 7.09 (2 H, d, J = 7),
7.37 (1 H, d, J = 9), 7.23–7.45 (6 H, m), 7.56 (2 H, d, J = 7.5), 7.75 (2
H, d, J = 7.5)
127.5, 127.7, 130.2, 130.6, 138.4, 141.3, 143.7,
147.9, 155.4
29b
29d
2.10 (3 H, s), 2.84–2.97 (2 H, m), 4.12 (1 H, t, J = 6.5), 4.36–4.39 (2 H, 21.1, 40.5, 47.2, 52.7, 66.9, 120.1, 125.0, 127.4,
m), 4.91 (1 H, m), 5.02 (1 H, m), 7.07–7.11 (2 H, m), 7.24–7.29 (10 H,
m), 7.33 (2 H, t, J = 7.5), 7.44–7.47 (2 H, m), 7.69 (2 H, d, J = 7.5)
127.5, 127.8, 129.1, 129.5, 130.3, 130.8, 135.3,
138.5, 141.4, 143.4, 143.8, 155.5
0.88 (3 H, d, J = 5), 0.89 (3 H, d, J = 5), 1.28–1.32 (1 H, m), 1.56–1.61 20.9, 21.8, 22.7, 24.5, 43.1, 47.1, 49.7, 66.8, 119.8,
(2 H, m), 2.22 (3 H, s), 4.15 (1 H, t, J = 6.5), 4.40 (2 H, d, J = 6.5), 4.81 124.7, 126.9, 127.6, 130.1, 130.5, 141.2, 143.6,
(2 H, m), 7.04 (2 H, d, J = 7.5), 7.18–7.27 (4 H, m), 7.33 (2 H, t, J = 7), 144.8, 155.4
7.51 (2 H, d, J = 7), 7.69 (2 H, d, J = 7)
32a
32b
32d
1.22 (3 H, d, J = 6.5), 1.49 (9H, s), 2.37 (3 H, s), 4.19–4.22 (1 H, m), 4.23 18.2, 21.5, 28.5, 47.3, 50.2, 64.5, 66.9, 80.6, 119.9,
(1 H, t, J = 6.5), 4.37–4.40 (1 H, m), 4.47–4.51 (1 H, m), 4.62 (1 H, br d, 123.3, 125.0, 127.0, 127.7, 130.1, 134.5, 139.9,
J = 7.5), 5.13 (1 H, br d, J = 7), 5.86 (1 H, br d, J = 7.5), 7.20–7.25 (4 H, 141.2, 143.7, 155.4, 156.3, 198.8
m), 7.29–7.33 (2 H, m), 7.38–7.41 (2 H, m), 7.60 (2 H, d, J = 7.5), 7.76
(2 H, d, J = 7.5)
1.44 (9H, s), 2.29 (3 H, s), 2.85 (1 H, dd, J = 14, 9), 2.96 (1 H, dd, J =
14, 6), 4.07 (1 H, t, J = 7), 4.19–4.24 (1 H, m), 4.27 (2 H, d, J = 6.5), 4.55 119.9, 123.6, 125.0, 126.9, 127.6, 127.9, 128.7,
(1 H, brd, J = 8), 4.97 (1 H, d, J = 8.5), 5.95 (1 H, d, J = 8), 7.14–7.16 129.2, 130.1, 134.5, 136.6, 139.9, 141.2, 143.7,
21.3, 28.3, 29.6, 38.3, 47.1, 55.6, 62.0, 67.0, 80.6,
(6 H, m), 7.18–7.22 (5 H, m), 7.28–7.33 (2 H, m), 7.38 (1 H, d, J = 7.5), 155.2, 156.7, 199.9
7.46 (1 H, d, J = 7.5), 7.64–7.68 (2 H, m)
0.84 (6 H, d, J = 6.5), 1.46 (9 H, s), 1.30–1.40 (1 H, m), 1.52–1.59 (2 H, 21.4, 21.8, 23.2, 24.8, 28.5, 41.1, 47.4, 52.5, 64.1,
m), 2.30 (3 H, s), 4.04–4.08 (1 H, m, 4.17 (1 H, t, J = 7), 4.38 (1 H, dd, 66.9, 80.6, 120.1, 123.7, 125.1, 127.2, 127.8, 130.2,
J = 10.5, 7), 4.45 (1 H, dd, J = 10.5, 7.0), 4.52 (1 H, brd, J = 8.5), 4.78 134.6, 139.9, 141.4, 143.9, 155.5, 156.9, 199.5
(1 H, d, J = 9), 5.80 (1 H, d, J = 8), 7.13–7.17 (4 H, m), 7.22–7.26 (2 H,
m), 7.33 (2 H, t, J = 7.5), 7.53 (2 H, d, J = 7.5), 7.69 (2 H, d, J = 7.5)
33aa
33ba
1.02 (3 H, d, J = 7), 1.37 (9H, s), 3.93–3.96 (1 H, m), 4.14 (1 H, dd, J = 16.3, 28.2, 46.7, 48.6, 58.5, 62.9, 65.2, 78.1, 120.1,
8, 6.5), 4.16–4.20 (2 H, m), 4.25–4.29 (1 H, m), 6.96 (1 H, d, J = 9), 7.28 125.2, 127.0, 127.6, 140.7, 143.3, 154.8, 155.9,
(1 H, m), 7.28–7.33 (2 H, m), 7.39 (2 H, t, J = 7), 7.67 (2 H, d, J = 7.5), 172.2
7.87 (2 H, d, J = 7.5)
1.46 (9H, s), 2.76–2.86 (2 H, m), 4.09–4.12 (1 H, m), 4.15–4.20 (2 H, m), 28.2, 36.8, 46.6, 54.0, 57.3, 65.5, 78.1, 120.0, 125.4,
4.17–4.20 (1 H, m), 4.24–4.27 (1 H, m), 6.99 (1 H, m), 7.20 (1 H, m),
125.9, 127.6, 127.9, 128.1, 129.2, 137.5, 140.6,
7.24–7.40 (7H, m), 7.44–7.48 (2 H, m), 7.68 (2 H, t, J = 6.5), 7.93 (2 H, 143.7, 155.5, 155.6, 172.6
d, J = 7.5)
Synthesis 2002, No. 15, 2296–2308 ISSN 0039-7881 © Thieme Stuttgart · New York