63
H, N). 13f (60% yield), m.p. 77–79 °C, 1H-NMR
(CDCl3) δ 1.02 and 1.11 (2t, 6H, J = 7.2 Hz), 1.53–1.98
(m, 4H), 2.26 (s, 3H), 5.49 (s, 1H), 6.90–7.85 (m, 4H).
Anal. C15H191FN2O2 (C, H, N). 13h (43% yield), m.p.
125–126 °C, H-NMR (CDCl3) δ 1.09 and 1.11 (2t, 6H,
J = 7 Hz), 1.62–1.91 (m, 4H), 2.27 (s, 3H), 5.51 (s, 1H),
6.35 (br, 1H), 7.09 (s, 1H), 7.22–7.42 (m, 10H), 7.68 and
8.11 (2d, 4H, J = 8.8 Hz). Anal. C29H30N2O4 (C, H, N).
4.46 (d, 2H, J = 5.6 Hz), 5.90 (s, 1H), 6.84 (br, 1H),
7.20–7.75 (m, 10H). Anal. C24H29N3O3 (C, H, N). 3d
(47% yield), m.p. 70–71 °C, H-NMR (CDCl3) δ 1.02
1
and 1.06 (2t, 6H, J = 7 Hz), 1.53–1.85 (m, 4H), 4.44 (d,
2H, J = 5.6 Hz), 5.94 (s, 1H), 6.81 (br, 1H), 7.24–7.51 (m,
15H). Anal. C28H29N3O3 (C, H, N). 3e (53% yield), m.p.
1
122–124 °C, H-NMR (CDCl3) δ 1.01 and 1.03 (2t, 6H,
J = 7.2 Hz), 1.55–1.99 (m, 4H), 4.47 (d, 2H, J = 5.6 Hz),
5.86 (s, 1H), 6.80–7.84 (m, 10H), 8.09 (s, 1H). Anal.
C22H24FN3O3 (C, H, N). 3f (55% yield), m.p. 83–85 °C,
1H-NMR (CDCl3) δ 1.01 and 1.03 (2t, 6H, J = 7.2 Hz),
1.52–1.98 (m, 4H), 2.25 (s, 3H), 4.44 (d, 2H, J = 5.6 Hz),
5.90 (s, 1H), 6.75–7.75 (m, 10H). Anal. C23H26FN3O3
(C, H, N). 3i (55% yield), m.p. 150–151 °C (3i.H2C2O4),
1H-NMR (CDCl3) δ 1.04 and 1.07 (2t, 6H, J = 7 Hz),
1.71–1.92 (m, 4H), 2.45–2.70 (m, 4H), 2.79 (t, 2H, J =
5.6 Hz), 3.50–3.70 (m, 4H), 4.12 (t, 2H, J = 5.6 Hz), 4.51
(d, 2H, J = 5.6 Hz), 5.86 (s, 1H), 6.85 (d, 2H, J = 8.8 Hz),
7.20–7.32 (m, 5H), 7.48 (d, 2H, J = 8.8 Hz), 8.07 (s, 1H).
Anal. C28H36N4O5 (C, H, N). 3l (62% yield), m.p.
6.1.2. General procedure for the preparation of the
(E)-4-(arylideneaminoxy)-2-azetidinones 13i and 13l
1 N NaOH (12.7 mL) was added to a stirred solution of
12i or 12l (3.7 mmol) in acetone (3.5 mL). After stirring
for 10 min at room temperature, a solution of 11
(3.3 mmol) in acetone (3.5 mL) was added, and the
resulting mixture was stirred at the same temperature for
40 min. The acetone was then removed in vacuo and the
aqueous layer was extracted with ether. The organic
phase was washed with brine, dried and evaporated to
give an oily residue which, after purification by MPLC on
C18 reversed phase using a 6:4 mixture of MeOH-H2O
with 8% of an aqueous solution of NH4OH (30%) and 4%
of 2-propanol, yielded the appropriate pure azetidinone
13i or 13l as oils. 13i (28% yield),1H-NMR (CDCl3) δ
1.06 and 1.08 (2t, 6H, J = 7 Hz), 1.64–1.86 (m, 4H),
2.45–2.70 (m, 4H), 2.85 (t, 2H, J = 5.6 Hz), 3.60–3.90
(m, 4H), 4.18 (t, 2H, J = 5.6 Hz), 5.50 (s, 1H), 6.43 (br,
1H), 6.93 (d, 2H, J = 8.8 Hz), 7.53 (d, 2H, J = 8.8 Hz),
8.12 (s, 1H). Anal. C20H29N3O4 (C, H, N). 13l (31%
yield),1H-NMR (CDCl3) δ 1.07 and 1.10 (2t, 6H, J = 7
Hz), 1.62–1.81 (m, 4H), 2.23 (s, 3H), 2.45–2.60 (m, 4H),
2.80 (t, 2H, J = 5.6 Hz), 3.55–3.73 (m, 4H), 4.18 (t, 2H,
J = 5.6 Hz), 5.47 (s, 1H), 6.45 (br, 1H), 6.85 (d, 2H, J =
8.8 Hz), 7.51 (d, 2H, J = 8.8 Hz). Anal. C21H31N3O4 (C,
H, N).
1
155–157 °C (3l.H2C2O4), H-NMR (CDCl3) δ 1.05 and
1.08 (2t, 6H, J = 7 Hz), 1.64–1.80 (m, 4H), 2.30 (s, 3H),
2.50–2.70 (m, 4H), 2.75 (t, 2H, J = 5.6 Hz), 3.65–3.80
(m, 4H), 4.17 (t, 2H, J = 5.6 Hz), 4.52 (d, 2H, J = 5.6 Hz),
5.95 (s, 1H), 6.85 (d, 2H, J = 8.8 Hz), 7.25–7.32 (m, 5H),
7.56 (d, 2H, J = 8.8 Hz). Anal. C29H38N4O5 (C, H, N).
1
14h (83% yield), m.p. 112–113 °C, H-NMR (CDCl3) δ
1.01 and 1.04 (2t, 6H, J = 7 Hz), 1.61–1.89 (m, 4H), 2.29
(s, 3H), 4.51 (d, 2H, J = 5.6 Hz), 5.51 (s, 1H), 6.87 (br,
1H), 7.09 (s, 1H), 7.22–7.42 (m, 5H), 7.68 and 8.11 (2d,
4H, J = 8.8 Hz). Anal. C37H37N3O5 (C, H, N).
6.1.4. (E)-4-(arylideneaminoxy)-1-N-
(benzylaminocarbamoyl)-2-azetidinone 3h
Trifluoroacetic acid (2 mL) was added dropwise to a
stirred and cooled solution of 14h (0.30 g, 0.5 mmol) in
anisole (4 mL) and the resulting mixture was stirred at
0 °C for 4 h and extracted with an ice-cooled 10%
aqueous NaHCO3 solution (3 × 25 mL). The aqueous
layer, after being washed with CHCl3 (2 × 30 mL), was
acidified to pH 3.5 at 0 °C by the addition of 10%
aqueous H3PO4 and then extracted with CHCl3 (3 ×
30 mL). Evaporation of the washed (brine) organic ex-
tracts yielded a white solid residue, which, after crystal-
lisation with AcOEt-hexane, gave pure 3h: 0.12 g as a
white solid (72% yield), m.p. 144–145 °C, 1H-NMR
(CDCl3) δ 1.09 and 1.10 (2t, 6H, J = 7 Hz), 1.74–2.03 (m,
4H), 2.35 (s, 3H), 4.53 (d, 2H, J = 5.6 Hz), 6.05 (s, 1H),
6.98 (br, 1H), 7.33–7.41 (m, 5H), 7.72 and 8.04 (2d, 4H,
J = 8 Hz). Anal. C24H27N3O5 (C, H, N).
6.1.3. General procedure for the preparation of the
(E)-4-(arylideneaminoxy)-1-N-(benzylaminocarbamoyl)-
2-azetidinones 3c–f, 3i–l and 14h
A stirred solution of the appropriate azetidinone 13
(1 mmol), Et3N (0.14 mL, 1 mmol) and a catalytic
amount of 4-(dimethylamino)pyridine (DMAP, 2 crys-
tals) in anhydrous CH2Cl2 (5 mL), was treated under
nitrogen with benzylisocyanate (0.37 mL, 3 mmol), and
the mixture was stirred at room temperature for 24 h. The
solvent was evaporated and the residue was purified by
crystallisation with i-PrOH (in the case of 3c–f and 14h)
or by MPLC on C18 reversed phase using a 6:4 mixture of
MeOH-H2O with 8% of an aqueous solution of NH4OH
(30%) and 4% of 2-propanol (in the case of 3i–l). 3c
1
(62% yield), m.p. 94 °C, H-NMR (CDCl3) δ 0.94–1.25
(m, 9H), 1.64–1.86 (m, 4H), 2.77 (q, 2H, J = 7.2 Hz),