Celite. Removal of solvent in vacuo and purification by column
chromatography on silica (hexane to 20% EtOAc–hexane)
afforded pure β-hydroxy ester 42 (7 mg, 60%). νmax/cmϪ1 3441,
3059, 2934, 1774, 1743, 1601, 1508, 1361, 1199, 1059 and 752;
δH 7.35–6.95 (5 H, m, Ph), 4.54 (1 H, d, J 2, NCH), 4.35–4.12
(3 H, m, OCH2CH3 and CHOH), 3.10 (1 H, br s, OH), 2.64–
2.45 (2 H, m, CH2), 2.12–1.62 (2 H, m, CH2), 1.78 (3 H, s, CH3)
and 1.30 (3 H, t, J 9, OCH2CH3); δC 170.16, 154.21, 137.01,
129.28, 122.37, 115.82, 76.06, 66.38, 61.54, 60.28, 28.19, 24.35,
23.56 and 14.12; m/z 304 (LRMS).
d, J 12, OCH2), 3.88 (1 H, d, J 12, OCH2), 2.48 (3 H, s, CH3),
1.85 (3 H, s, CH3); m/z 250 (LRMS).
Acknowledgements
A. N. and G. R. D. thank the Council of Scientific and
Industrial Research (1/1431/96/EMR-II) and the Department
of Science and Technology (SP/S1/G-19/94) for financial assis-
tance. A. K. K. and H. L. C. acknowledge support from
NIH Grant CA-10925. P. S. C. is the recipient of fellowship
from the Department of Atomic Energy.
Aza-carbacepham 47
To a solution of unsaturated ester 40 (7 mg, 0.025 mmol) in
2 cm3 of EtOAc was added 10% Pd/C (5 mg), the mixture
was flushed with H2 and then stirred at room temperature
under a H2 atmosphere for 4 h. The reaction mixture was
filtered through Celite. Work up afforded 6 mg of crude
aza-carbacepham 47 which was purified by column chromato-
graphy on silica (hexane to 20% EtOAc–hexane) (6 mg, 86%).
νmax/cmϪ1 2936, 2863, 1771, 1732, 1601, 1508, 1354, 1194 and
752; δH 7.35–6.95 (5 H, m, Ph), 4.59 (1 H, dd, J 8, 4, NCH),
4.28–4.12 (2 H, m, OCH2), 2.28–1.55 (4 H, m, 2 × CH2), 1.71
(3 H, s, CH3) and 1.30 (3 H, t, J 9, CH3); δC 171.91, 153.29,
137.19, 122.29, 115.80, 61.25, 51.87, 35.16, 26.87, 23.33, 17.13
and 14.17; m/z 288 (LRMS).
References
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3-Hydroxy-aza-carbacephem 48
β-Hydroxy ester 42 (12 mg, 0.04 mmol) in 1 cm3 of acetone
was cooled to 0 ЊC, Jones reagent (100 µl, 0.8 mmol, 8 )
was added and stirring continued for 2 h at 0 ЊC to room
temperature. The reaction mixture was diluted with brine and
extracted with diethyl ether. Work up provided a 1:1 mixture
of keto–enol isomers which when left at room temperature for
2 days afforded enol 48 which was purified by chromatography
4 B. G. Spratt, Science, 1994, 264, 388.
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on silica (hexane to 40% EtOAc–hexane) (11 mg, 88%). νmax
/
cmϪ1 3418, 2924, 2855, 1807, 1749, 1694, 1601, 1506, 1352, 1256
and 1157; δH 11.64 (1 H, s, enol H), 7.42–7.06 (5 H, m, Ph), 4.44
(2 H, q, J 9, OCH2), 2.94–2.05 (4 H, m, 2 × CH2), 2.00 (3 H,
s, CH3), 1.66 (3 H, s, CH3) and 1.42 (3 H, t, J 9, OCH2CH3);
m/z 208 (LRMS).
6 (a) J. E. Baldwin, R. M. Adlington, R. H. Jones, C. J. Schofield,
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Methyl enol ether 49
Diazomethane was generated by adding N-nitroso-N-methyl-
urea (200 mg, 2 mmol) to a solution of 50% aq. KOH (20 cm3)
in 10 cm3 of diethyl ether at 0 ЊC, the solution was left for a few
minutes till the yellow colour developed. The diethyl ether layer
was distilled and CH2N2 was bubbled through a solution of
enol 48 (12 mg, 0.04 mmol) in 10 cm3 of distilled diethyl ether at
0 ЊC. When the solution turned yellow it was slowly warmed to
room temperature and left to dry. The crude methyl enol ether
49 was purified by column chromatography on silica (hexane to
20% EtOAc–hexane) (8 mg, 63%). νmax/cmϪ1 2938, 1807, 1742,
1601, 1510, 1445, 1352, 1257, 1091, 754 and 692; δH 7.42–7.12
(5 H, m, Ph), 4.45 (2 H, q, J 9, OCH2), 3.60 (3 H, s, OCH3),
2.90–2.36 (4 H, m, 2 × CH2), 2.00 (3 H, s, CH3) and 1.42 (3 H,
t, J 9, CH3); δC 172.06, 159.54, 135.07, 129.69, 129.35, 124.56,
116.54, 115.96, 82.54, 63.17, 51.87, 30.21, 27.75, 22.45, 13.85;
m/z 317 (LRMS).
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Phenolic alcohol 52
Through a solution of alkene (100 mg, 0.5 mmol) in 20 cm3 of
CH2Cl2 was passed a stream of ozone at Ϫ78 ЊC until the light
blue colour persisted. The reaction mixture was flushed with
oxygen for 5 min, NaBH4 (76 mg, 2 mmol) added at 0 ЊC and
stirring continued for 1 h at 0 ЊC. The reaction mixture was
acidified with 5% aq. HCl to pH 4 and extracted with diethyl
ether. Work-up and purification by column chromatography on
silica (hexane to 50% EtOAc–hexane) afforded pure phenolic
alcohol 52 (50 mg, 40%). δH 7.42–6.88 (5 H, m, Ph), 4.42 (1 H,
J. Chem. Soc., Perkin Trans. 1, 1998
2607